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  • A Feasibility Study of E7 TCR-T Cell Induction Therapy for Locoregionally Advanced HPV-Associated Cancers. - NCT05639972

    Primary Objective: - To determine the feasibility of administering E7 TCR-T cell therapy as induction treatment for LAHPVC Secondary Objectives: - To determine the objective tumor response rate at 6-weeks after treatment - To assess 2-year and 5-year disease free survival (DFS) - To collect biospecimens for exploratory translational research

    View All Details

    • Protocol Number:
      192104

    • Principal Investigator:
      Christian Hinrichs

    • Phase:
      Phase I

    • Scope:
      Local

    • Applicable Disease Sites:
      Breast ,Cervix ,Lip, Oral Cavity and Pharynx ,Other Female Genital ,Other Male Genital ,Stomach

    • Therapies Involved:
      Immunotherapy

    • Drugs Involved:
      TCR-T Cell infusion

    Read Inclusion & Exclusion Criteria

    Inclusion Criteria: Subjects must meet all the following criteria to participate in this

      study. 1. Histologically confirmed carcinoma of a primary tumor site and stage indicated in Table 3 of the protocol. 2. Tumor with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. 3. HLA-A*02:01 allele determined by testing performed in a CLIA certified laboratory. Participants may be enrolled based on low resolution typing (i.e., HLA-A*02) but the HLA-A*02:01 allele type must be confirmed prior to apheresis. 4. Measurable disease per RECIST Criteria Version 1.1 or PERCIST. 5. Age ≥ 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. 7. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy test is not required for women who have had a bilateral oophorectomy or hysterectomy. 8. Men and women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control, abstinence, tubal ligation, or vasectomy) prior to study entry and for four months after treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. 9. Seronegative for HIV antibody, hepatitis B surface antigen (HBsAg), and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by reverse transcription polymerase chain reaction (RT-PCR) must be negative. 10. Participants must have organ and marrow function as defined below: 1. Leukocytes > 3,000/mcL 2. Absolute neutrophil count > 1,500/mcL 3. Platelets > 100,000/mcL 4. Hemoglobin > 9.0 g/dL 5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL. 6. Serum aspartate aminotransferase (AST) (SGOT)/ alanine transaminase (ALT) (SGPT) < 2.5 x upper limit of normal (ULN) 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or aPTT within therapeutic range and no history of severe hemorrhage. 11. Participants must be able to understand and be willing to sign the written informed consent document. 12. Participants must agree to participate in Rutgers protocol 192103 (Pro2021002307) for gene therapy long term follow up and in Rutgers protocol 192002 (Pro2021000281) for biospecimen studies.Note: Patients may have undergone minor surgical procedures with the past three weeks, aslong as all toxicities have recovered to Grade 1 or less.

    Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from

      participation in this study: 1. Have received prior systemic therapy or definitive chemoradiation for the cancer that is being treated on this protocol. Palliative radiation therapy for symptom management, such as to control tumor-induced bleeding, is permitted. 2. Current treatment with another investigational agent. 3. History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study. 4. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements. 5. Subjects with HLA-A*02:01 damaging mutation or allele loss detected by research or clinical sequencing will not be eligible. 6. Documented LVEF of less than or equal to 45% tested. The following participants will undergo cardiac evaluations: 1. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or 2. Age ≥ 50 years old 7. Participants with baseline screening pulse oxygen level of ≤ 92% on room air will not be eligible. If the underlying cause of hypoxia improves, they may be reevaluated. 8. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study. 9. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment. 10. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 11. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible. 12. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to: 1. Carcinoma in situ 2. Cutaneous skin cancers requiring only local excision 3. Low grade non-muscle invasive bladder cancer 4. Low grade prostate cancer 13. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible. 14. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data.

    Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

    For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.

    • Rutgers Cancer Institute
  • A Phase 2 Study Using Chemoimmunotherapy with Gemcitabine, Cisplatin and Nivolumab in Newly Diagnosed Nasopharyngeal Carcinoma (NPC). - NCT06064097

    Primary Aim: - To evaluate safety of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC) by determining the rate of CTCAE Grade 3 or higher immune related adverse events (irAEs). Secondary Aims: - To estimate the 2-year event-free survival (EFS) of children, adolescents and young adults with NPC who are treated with Induction Chemoimmunotherapy (CIT), followed by Consolidation Chemoradioimmunotherapy (CRIT, cisplatin, nivolumab and response-adjusted, dose de-escalated radiation therapy), and nivolumab maintenance therapy. - To evaluate the objective response rate (ORR) including complete responders and partial responders (CR + PR) of neoadjuvant CIT. - To evaluate feasibility of combining chemotherapy (cisplatin and gemcitabine) with an anti-PD1 immune checkpoint inhibitor (nivolumab) in children, adolescents and young adults with nasopharyngeal carcinoma (NPC). - To evaluate the cumulative incidence of local and distant relapse.

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    • Protocol Number:
      112405

    • Principal Investigator:
      Scott A Moerdler

    • Phase:
      Phase II

    • Scope:
      National

    • Applicable Disease Sites:
      Lip, Oral Cavity and Pharynx

    • Therapies Involved:
      Chemotherapy multiple agents systemic Radiotherapy

    • Drugs Involved:
      CISPLATIN GEMCITABINE Opdivo (Nivolumab)

    Read Inclusion & Exclusion Criteria

    Inclusion Criteria:

    • Patients must be ≤ 21 years of age at the time of study enrollment
    • Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC)
    • Patients must have had histologic verification of the malignancy at original diagnosis
    • Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
    • Patients must have had histologic verification of the malignancy at original diagnosis
    • Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
    • Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of ≥ 60%
    • Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to start of protocol therapy)
    • Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to start of protocol therapy)
    • Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2 or (within 7 days prior to start of protocol therapy)
    • A serum creatinine based on age/sex (within 7 days prior to start of protocol therapy) Age: Maximum serum creatinine (mg/dL) 1 month to < 6 months: 0.4 mg/dL (male); 0.4 mg/dL (female) 6 months to < 1 year: 0.5 mg/dL (male); 0.5 mg/dL (female) 1 to < 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to < 10 years 1 mg/dL (male); 1 mg/dL (female) 10 to <13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) ≥ 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and (within 7 days prior to start of protocol therapy)
    • Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 135 U/L* (within 7 days prior to start of protocol therapy)
    • Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
    • Shortening fraction of ≥ 27% by echocardiogram, or
    • Ejection fraction of ≥ 50% by radionuclide angiogram
    • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination
    • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and T-cell count above the lower limit of normal are eligible for this trial
    • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

    Exclusion Criteria:

    • Patients who received prior radiotherapy to the head or neck
    • Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission
    • Patients with a diagnosis of immunodeficiency
    • Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • Note: Patients with well-controlled asthma and no need for systemic steroids for the treatment of asthma in the last 12 months will not be excluded
    • Patients with a condition requiring systemic treatment with either corticosteroids (> 0.25 mg/kg (10 mg) daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 0.25 mg/kg (10 mg) daily prednisone equivalent, are permitted in the absence of active autoimmune disease
    • Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
    • Patients with detectable viral load of human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or active tuberculosis
    • Patients who have undergone solid organ or allogeneic hematopoietic transplant at any time
    • Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
    • Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of nivolumab, 6 months after the last dose of gemcitabine, and 14 months after the last dose of cisplatin, whichever is longer
    • Males of childbearing potential that are sexually active must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of gemcitabine, and 11 months after the last dose of cisplatin, whichever is longer
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of nivolumab
    • All patients and/or their parents or legal guardians must sign a written informed consent
    • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

    Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

    For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.

    • Newark Beth Israel Medical Center
  • A Phase II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers. - NCT05686226

    The primary objective of this trial is to determine the objective tumor response rate (CR+PR) and duration of response for treatment of recurrent/refractory or metastatic HPV-associated cancers with E7 TCR-T cells.

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    • Protocol Number:
      192204

    • Principal Investigator:
      Christian Hinrichs

    • Phase:
      Phase II

    • Scope:
      Local

    • Applicable Disease Sites:
      Anus ,Cervix ,Larynx ,Lip, Oral Cavity and Pharynx ,Other Female Genital ,Other Male Genital

    • Therapies Involved:
      Immunotherapy

    • Drugs Involved:
      E7 TCR T cell

    Read Inclusion & Exclusion Criteria

    Inclusion Criteria: Subjects must meet all the following criteria to participate in this

      study. 1. Histologically or cytologically confirmed metastatic or refractory/recurrent HPV-16+ cancer. 2. Tumor and/or blood with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. 3. HLA-A*02:01 allele as determined by testing performed in a CLIA certified laboratory. Participants may be enrolled based on low resolution typing (i.e., HLA-A*02) but the HLA-A*02:01 allele type must be confirmed prior to apheresis. 4. Measurable disease as assessed by RECIST Criteria Version 1.1. 5. Age ≥ 18 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening. 7. Must have received prior first line standard therapy or have declined standard therapy. 8. Standard treatment options for first and second-line therapy must be presented and formally declined (Appendix VII). 9. Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients must be fully recovered from surgery. 10. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy test is not required for women who have had a bilateral oophorectomy or hysterectomy. 11. Men and women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control, abstinence, tubal ligation, or vasectomy) prior to study entry and for four months after treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. 12. Seronegative for HIV antibody, hepatitis B antigen (HBsAg), and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by RT-PCR for hepatitis C (HCV) RNA must be negative. 13. Participants must have organ and marrow function as defined below: 1. Leukocytes > 3,000/mcL 2. Absolute neutrophil count > 1,500/mcL 3. Platelets > 100,000/mcL 4. Hemoglobin > 9.0 g/dL 5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL. 6. Serum aspartate transferase (AST) (SGOT)/alanine transaminase (ALT) (SGPT) < 2.5 x upper limit of normal (ULN) 7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation). 8. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or aPTT within therapeutic range and no history of severe hemorrhage. 14. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells. Adverse events from prior therapy must have resolved to ≤ grade 1 according to CTCAE Version 5.0 or have demonstrated clinical stability for the protocol. 15. Participants must be able to understand and be willing to sign the written informed consent document. 16. Participants must agree to participate in Rutgers protocol 192103 (Pro2021002307) for gene therapy long term follow up and in Rutgers protocol 192002 (Pro2021000281) or NIH protocol 16C0061 (Rutgers 192202) for biospecimen collection study.Note: Participants may have undergone minor surgical procedures with the past threeweeks, as long as all toxicities have recovered to Grade 1 or less.

    Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from

      participation in this study: 1. Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements. 2. History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study. 3. History of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test. 4. Documented LVEF of less than or equal to 45% tested. The following participants will undergo cardiac evaluations: 1. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or 2. Age ≥ 50 years old 5. Participants with baseline screening pulse oxygen level of ≤ 92% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated. 6. Subjects with HLA-A*02:01 damaging mutation or allele loss detected by clinical or research genomic profiling will not be eligible. 7. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study. 8. Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment. 9. Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications). 10. Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible. 11. Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to: 1. Carcinoma in situ 2. Cutaneous skin cancers requiring only local excision 3. Low grade non-muscle invasive bladder cancer 4. Low grade prostate cancer Participants with prior or concurrent malignancy that do not meet the above criteria are excluded. 12. Subjects who received a live vaccine within 30 days prior to enrollment are not eligible. 13. Determination by the Principal Investigator that participation is not in the best interest of the research subject or may jeopardize the safety of the subject or integrity of the clinical trial data. 14. Current treatment with another investigational agent.

    Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

    For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.

    • Robert Wood Johnson University Hospital
  • Biomarkers of Oral Carcinogenesis and Oral Cancer Pain.

    Primary Objective: To identify biomarkers for cancer pain in biofluids and tissue of cancer patients with pain, compared to cancer patients without pain or patients with non malignant tumors, or normal patients. Secondary Objective: To identify epigenetic and gene expression biomarkers in tissues or biofluids that could differentiate between cancer, pre-cancer and normal/non malignancy patients.

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    • Protocol Number:
      032202

    • Phase:
      N/A

    • Scope:
      National

    • Applicable Disease Sites:
      Lip, Oral Cavity and Pharynx

    • Cooperman Barnabas Medical Center
    • Rutgers Cancer Institute
  • DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment. - NCT07158164

    Study Objectives: Primary Endpoint - Dose modification and safety of patients with one DPYD genetic variant (heterozygous DPYD deficiency) when starting at reduced fluoropyrimidine doses. Secondary Endpoints - To characterize the continued doses used in heterozygous patients with DPYD variants and their ability to increase or necessity to decrease doses further. - To characterize the specific grade and nature of fluoropyrimidine-related toxicity in all patient cohorts. - To determine Time to Progression (TTP) on first fluoropyrimidine treatment for all patients. - To compare rates of fluoropyrimidine dose reductions and dose intensity between DPYD variant patients and normal control patients.

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    • Protocol Number:
      072504

    • Principal Investigator:
      Howard Hochster

    • Phase:
      N/A

    • Scope:
      Local

    • Applicable Disease Sites:
      Breast ,Colon ,Esophagus ,Larynx ,Lip, Oral Cavity and Pharynx ,Other Digestive Organ ,Pancreas ,Rectum ,Small Intestine ,Stomach

    • Drugs Involved:
      5-Fluorouracil CAPECITABINE FOLFOX

    Read Inclusion & Exclusion Criteria

    Inclusion Criteria:

    • Diagnosis of cancer in either the adjuvant or metastatic setting requiring initial therapy with 5-FU or Capecitabine.
    • DPYD testing performed by a CLIA-certified laboratory (i.e., Guardant 360 or Caris blood testing for genomic profiling, DPYD testing by the Mayo Clinic or other certified laboratory) with results available before starting chemotherapy.
    • DPYD testing results falling into one of the following cohorts for first-line therapy with a fluoropyridine:
    • Study Cohort: Patients with one DPYD variant in one gene (heterozygotes).
    • Control Arm: Patients with normal or wild-type DPYD genes, for comparison, will be treated at the usual 100% dose.
    • -FOLFOX regimen (N=50)
    • ECOG Performance Status 0-2.
    • Measurable disease or non-measurable disease allowed, including adjuvant 5-FU-based regimens.

    Exclusion Criteria:

    • Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician.
    • Patients with two DPYD variants (homozygous deletions or non-functional genetic variants, or double heterozygotes with two different abnormalities) should not receive 5-FU or Capecitabine and are therefore excluded from the study.
    • Pregnant Women and Children

    Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

    For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.

    • Cooperman Barnabas Medical Center
    • Monmouth Medical Center
    • Clara Maass Medical Center
    • Community Medical Center
    • Newark Beth Israel Medical Center
    • Jersey City Medical Center
    • RWJ University Hospital Hamilton
    • RWJ University Hospital Somerset
    • Trinitas Regional Medical Center – Williamson Street Campus
  • Phase 1/1b Study of AKT Inhibitor Ipatasertib with Chemoradiation for Locally Advanced Head and Neck Cancer. - NCT05172245

    Primary Objectives: -To determine the MTD and recommended Phase 2 dose (RP2D) of ipatasertib in combination with definitive chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC) based on dose-limiting toxicities (DLTs). Secondary Objectives: - To assess acute and late toxicities, based on CTCAE version 5.0. Toxicities occurring >90 days from the end of radiation therapy will be considered late toxicities. - To assess long-term swallowing function, based on gastric tube dependency at 6 and 12 months that is different from baseline. - To determine duration and completion rate of prescribed radiation and chemotherapy. - To determine pharmacokinetic profile of ipatasertib in combination with cisplatin and radiation therapy, based on peak and trough blood levels in patients administered ipatasertib orally. - To determine pharmacodynamic effects of ipatasertib at the MTD, based on pAKT, pS6 and pPRAS40 as markers of AKT pathway inhibition, and gamma-H2AX as a marker of radiosensitization. - To observe and record anti-tumor activity (objective response rate by RECIST criteria, locoregional control, relapse-free survival, and overall survival) of the combination of ipatasertib, cisplatin, and radiation therapy in patients with HNSCC. Although the clinical benefit of this combination has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. - To correlate efficacy outcomes with tumor genotype, based on whole exome sequencing of pre-treatment biopsy specimens.

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    • Protocol Number:
      032204

    • Phase:
      Phase I

    • Scope:
      National

    • Applicable Disease Sites:
      Larynx ,Lip, Oral Cavity and Pharynx

    • Therapies Involved:
      Chemotherapy single agent systemic Radiotherapy

    • Drugs Involved:
      Ipatasertib

    Read Inclusion & Exclusion Criteria

    Inclusion Criteria:

    • Patients must have pathologically confirmed HNSCC (including tumors of the oropharynx, hypopharynx, larynx, oral cavity, nasal cavity, maxillary and other paranasal sinuses, and unknown primary of the head and neck), with measurable disease as per RECIST 1.1
    • Oropharyngeal and unknown primary squamous cell cancers must test for human papilloma virus (HPV), for example by p16 immunohistochemistry (IHC), in situ hybridization (ISH), or polymerase chain reaction (PCR). HPV testing is not required for other HNSCC primary tumor sites
    • Patients with p16-positive tumors are eligible if M0 and any of one the following: cT4 or cN3 or cT2-3N2 or imaging-detected extranodal extension (iENE) according to the American Joint Committee on Cancer (AJCC)/TNM Staging System, 8th or 9th edition (Ed.)
    • Patients with p16-negative (or not tested) tumors are eligible if clinical stage III-IVB (locally advanced but non-metastatic) according to the AJCC/TNM Staging System, 8th or 9th Ed.
    • Must be candidate for concurrent, definitive cisplatin and radiation therapy as judged by the treating physician
    • Able to swallow tablets at the time of enrollment
    • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ipatasertib in combination with chemoradiation in patients < 18 years of age, children are excluded from this study
    • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
    • Life expectancy of greater than 3 months
    • Absolute neutrophil count >= 3000/mcL
    • Hemoglobin >= 10 g/dL
    • Platelets >= 150,000/mcL
    • Serum albumin >= 3 g/dL
    • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN / 2 x institutional ULN
    • Alkaline phosphatase (ALP) =< 2.0 x institutional ULN
    • Partial thromboplastin time (PTT) (or activated [a]PTT) and international normalized ratio (INR) =< 1.5 institutional ULN (except for patients receiving anticoagulation therapy)
    • Creatinine clearance (CLcr) > 60 mL/min
    • For this calculation, use the Cockroft-Gault formula
    • Fasting glucose =< 150 mg/dL (8.3 mmol/L) and (when indicated) glycosylated hemoglobin (HbA1c ) =< 7.5% (58 mmol/mol)
    • Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy with undetectable viral load within 6 months
    • Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative hepatitis B virus surface antigen [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV deoxyribonucleic acid [DNA] test) are eligible. Patients with chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy, if indicated. Patients undergoing current treatment with anti-viral therapy for HBV are ineligible
    • Patients with a history of hepatitis C virus (HCV) infection are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
    • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
    • The effects of ipatasertib on the developing human fetus are unknown. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib and agreement to refrain from donating eggs during this same period. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 28 days after the last dose of ipatasertib
    • Ability to understand and the willingness to sign a written informed consent document
    • For the expansion cohort only, there is a mandatory ask of patients to consider undergoing on-treatment biopsies

    Exclusion Criteria:

    • Primary tumor of nasopharynx, salivary, thyroid or parathyroid glands, or skin
    • Distant metastases from the current HNSCC
    • Prior treatment (e.g., chemotherapy, radiation, or definitive surgery) for the current locally advanced HNSCC is not permitted. Biopsies, including those performed under anesthesia, are not considered surgery. Patients who underwent prior definitive surgery alone for an early stage (T1-2N0) HNSCC which has now recurred with stage III-IVB disease at least 3 months after the initial surgery are eligible
    • For patients with a prior history of another malignancy, no prior chemotherapy or radiation may have been administered within 6 weeks prior to study entry. Among patients who received prior radiation to the head and neck or adjacent anatomical site for another malignancy, there may be no overlap with current area to be irradiated
    • Current use of any other investigational agents
    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib or other agents used in study
    • Treatment with strong inhibitors or inducers of CYP3A4 or P-glycoprotein within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
    • Patients with uncontrolled intercurrent illness, including active infection
    • Pregnant women are excluded from this study because ipatasertib is an oral AKT inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipatasertib, breastfeeding should be discontinued if the mother is treated with ipatasertib. These potential risks may also apply to other agents used in this study
    • Patients with type I or type II diabetes mellitus requiring insulin at study entry. Patients with non-insulin dependent type II diabetes mellitus are eligible, as are patients who are on a stable dose of oral diabetes medication >= 4 weeks prior to initiation of study treatment. Patients with a history of diabetes mellitus, an abnormal fasting glucose level, or other signs or symptoms indicating diabetes mellitus, must meet the laboratory eligibility criteria for fasting blood glucose and hemoglobin A1c
    • History of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
    • History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
    • Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
    • Known clinically significant history of liver disease consistent with Child Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), or cirrhosis
    • Grade >= 2 uncontrolled or untreated hypercholesterolemia (cholesterol > 300 mg/dL or > 7.75 mmol/L) or hypertriglyceridemia (triglycerides > 300 mg/dL or > 3.42 mmol/L)

    Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site www.clinicaltrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.

    For further information about clinical trials, please contact us at 732-235-7356 or 844-CANCERNJ.