Primary:
- To assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone in patients with biliary tract cancers (BTC) who have received one systemic therapy for advanced disease, as measured by Overall Response Rate (ORR) assessed by an Independent Central Radiology (ICR) review.
Secondary:
- To assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone in patients with BTC as measured by Disease Control Rate (DCR), assessed by an ICR review.
- To assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone in patients with BTC as measured by Duration of Response (DOR), assessed by an ICR review.
- To assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone in patients with BTC as measured by Progression Free Survival (PFS).
- To assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone in patients with BTC as measured by Overall Survival (OS).
- To evaluate the safety profile of CTX-009 in combination with paclitaxel.
- To assess the Quality of Life (QoL), as measured using the EORTC QLQ-C30 and BIL21, in patients with BTC treated with CTX-009 in combination with paclitaxel vs. paclitaxel alone.
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Protocol Number:
072214
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Principal Investigator:
Howard Hochster M.D
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Phase:
Phase II/III
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Scope:
National
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Applicable Disease Sites:
Other Digestive Organ
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Therapies Involved:
Chemotherapy single agent systemic
Chemotherapy multiple agents systemic
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Drugs Involved:
PACLITAXEL
CTX-009
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Contacts:
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Rutgers University
Prinicipal Investigator:
Howard Hochster M.D
Read Inclusion & Exclusion Criteria
INCLUSION CRITERIA 1. 18 years of age or older 2. Histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma) 3. Patients must have radiologically documented progression after a prior gemcitabine and platinum containing chemotherapy regimen as initial therapy for locally advanced or metastatic disease. Patients who subsequently receive additional systemic treatment are not eligible. Patients who relapse within 6 months of receiving a gemcitabine and platinum containing chemotherapy regimen in the adjuvant setting are also eligible 4. At least one lesion measurable as defined by RECIST v1.1 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 6. Predicted life expectancy of at least 12 weeks 7. No evidence of ongoing infection and adequate biliary excretion or patients whose adequate biliary excretion can be confirmed with the following procedures: 1. Patients who underwent endoscopic retrograde biliary drainage (ERBD) at least 1 week before the investigational drug treatment 2. Patients with endobiliary stents are eligible, provided there is no evidence of obstruction 3. Patients free of any signs of active or suspected uncontrolled infection after a drainage procedure 4. Patients free of any risk of hemorrhage and with incision completely healed 8. Adequate bone marrow, hepatic, and renal function within 14 days of randomization as described below. (Patient must be free of G-CSF treatment and blood transfusion within 14 days prior to the lab test): 1. Absolute neutrophil count (ANC) ≥ 1,500/mm3 2. Hemoglobin ≥ 9.0 g/dL 3. Platelet count ≥ 100,000/mm3 4. Total bilirubin ≤ 1.5 X ULN 5. AST/ALT ≤ 3.0 X ULN (≤5 X ULN in case of hepatic metastasis) 6. Estimated creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault 7. Urine protein ≤ 1+ by Dipstick (Only when urinalysis shows a protein dipstick result of > 1 positive (+), the total protein volume (<1.0 g/24hr) can be confirmed with a 24-hour urine test.) 8. Serum amylase and lipase level ≤ 1.5 X ULN 9. Serum Albumin ≥ 3.0 g/dL 9. Female patients who are women of childbearing potential (WCBP) must have a negative pregnancy test (serum-hCG or urine-hCG performed at the Investigator's discretion) within 14 days of randomization 10. Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commit to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 6 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment. 11. Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before any protocol-directed screening procedures are performed EXCLUSION CRITERIA 1. Patients who are eligible to be treated with a molecularly targeted therapy on a labelled regimen after receiving first-line chemotherapy 2. From the time point of screening, 1. Less than 4 weeks have elapsed since patients had a surgery or major procedure 2. Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy 3. Patients with percutaneous transhepatic biliary drains (PTBD) 4. Prior to the initial treatment of study drug, 1. Less than 2 weeks have elapsed since patients had chemotherapy or hormone therapy 2. Less than 2 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment 3. Less than 4 weeks since radiation therapy, cryotherapy, radiofrequency ablation, anhydrous alcohol therapy, or photodynamic therapy, including TACE and TARE 5. A history of the following cardiovascular diseases in past 5 years: 1. Congestive heart failure (CHF) that corresponds to Class II or a higher class (or less than 50% of left ventricular ejection fraction (LVEF)) under New York Heart Association (NYHA) classification 2. Uncontrolled hypertension (SBP/DBP >140/90 mmHg) (e.g., patient with SBP/DBP >140/90 mmHg despite the best care including optimizing the antihypertensive medication regimen) 3. Patients with any history of hypertensive crisis or pre-existing hypertensive encephalopathy 4. Pulmonary hypertension 5. Myocardial infarction 6. Uncontrolled arrhythmia 7. Unstable angina 8. Patients with any significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to the initial treatment of the investigational product 6. History of hypersensitivity reactions to any components of the investigational product or other drugs of the same class (humanized/human monoclonal antibody drugs) or paclitaxel 7. Patients with contraindications to paclitaxel therapy 8. Patients with persistent, clinically significant toxicities (excluding hair loss) from previous anticancer treatment that corresponds to Grade 2 or a higher grade under NCI-CTCAE v5.0 9. Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis that have been treated with either surgery or radiation can participate provided that systemic corticosteroid treatment was discontinued at least 4 weeks prior to screening and that the patient is radiologically and neurologically stable or improving) 10. A history of the following hemorrhage-related or gastroenterological disease: 1. Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor in great arteries 2. History of clinically significant gastroenterological disease, such as peptic ulcer, GI bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms, and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease (IBD) 11. Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant drugs (warfarin, heparin, etc.) within 2 weeks prior to randomization, or is expected to need those drugs during the clinical study 12. Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted): 1. NSAIDs: Up to 3 consecutive days' use is permitted. 2. Corticosteroids: Topical use of corticosteroids, such as topical intra-articular injection, intranasal administration, eye drops, inhaler, etc., or temporary systemic corticosteroid use for treatment and prevention of patient's contrast media allergy, paclitaxel pre-treatment, or adverse event, is permitted 13. Severe infection requiring ongoing systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases 14. Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with positive HBsAg and/or detectable HBV DNA are eligible only if adequately controlled on antiviral therapy according to institutional standards and liver function eligibility criteria are also met. HCV patients showing sustained viral response or patients with immunity to HBV infection may enroll. 15. Patients with other severe diseases or uncontrolled illnesses that warrant the exclusion from the study (permitted only if medically controlled) including but not limited to: 1. Pre-existing hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to screening 2. Major, unhealed injury, active ulcer, or untreated fracture 3. Pre-existing conditions of cerebrovascular incident (ischemic or hemorrhagic stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months prior to screening. 4. Moderate to severe ascites and/or pleural effusion. However, enrollment is permitted for patients with ascitic fluid as long as paracentesis is not required to improve the condition. 5. Interstitial lung disease or pulmonary fibrosis 16. Patients expected to require anticancer treatment other than the investigational product during the clinical study 17. Pregnant or lactating patients, or patients planning to become pregnant during the clinical study 18. A history of primary malignant tumor other than BTC with the following exceptions: 1. At least 3 years have passed since complete remission of primary malignant tumor (Patients who had papillary thyroid carcinoma and underwent a radical resection may participate in the clinical study even if less than 3 years have elapsed). 2. At least 1 year has passed since complete resection of dermal basal cell carcinoma or successful treatment of cervical intraepithelial neoplasia 19. Clinically significant abnormal ECG findings or history determined as clinically significant by the Investigator 20. QT interval (Fridericia's formula) (QTcF) interval > 450msec at the time of screening
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.