Study investigates whether ramucirumab or merestinib in combination with cisplatin and gemcitabine can help patients with biliary tract cancer.

Phase 1

• Conditions: Advanced or Metastatic Biliary Tract Cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004699-31-BE
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-02-16
• Last Update Posted: 21 July 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 364

Inclusion Criteria

[1]Are of an acceptable age to provide informed consent according to the local regulations and are at least 18 years of age.
[2]Have an estimated life expectancy =3 months.
[3]Have an Eastern Cooperative Oncology Group performance status of 0 or 1 at the time of randomization (refer to Appendix 7).
[4]Have a histologically or cytologically confirmed diagnosis of non-resectable, recurrent, or metastatic biliary tract adenocarcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or Ampulla of Vater).
[5]Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) assessments performed = 28 days prior to Cycle 1 Day 1.
[6]Have resolution of all clinically significant toxic effects of prior therapy to Grade =1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.
[7]Have adequate biliary drainage (per investigator’s discretion), with no evidence of ongoing infection.
[8]Have adequate organ function as determined by:
a. Hepatic: Total bilirubin, aspartate transaminase (AST), and alanine transaminase (ALT) are all = 3 times upper limit of institutional normal value (ULN) on 2 measurements separated by at least 5 days.
b. Renal:
i. Glomerular filtration rate (GFR) of =50 ml/min/1.73 m2. GFR should be calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (refer to Appendix 6), or may be measured using 24 hour urine collection or clearance of exogenous filtration markers (such as iothalamate or 51-CrEDTA or Tc99m-DTPA).
ii. The patient’s urinary protein is =1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria =2+, then a 24-hour urine must be collected and must demonstrate <2 g of protein in 24 hours to allow participation in the study.
c. Hematologic:
i. Absolute neutrophil count (ANC) =1.5 x 109/L,
ii. hemoglobin =9 g/dL (5.58 mmol/L; packed red blood cell transfusions are not allowed within 1 week prior to baseline hematology profile), and
iii. platelets = 100 x 109/L.
d. Coagulation: The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) =1.5 and a partial thromboplastin time (PTT/aPTT) =5 seconds above the ULN. Patients receiving low-dose anticoagulant therapy at prophylactic doses (such as prophylaxis with low-molecular weight heparin) are eligible, provided that INR =1.5 and PTT/aPTT =5 seconds above the ULN. Treatment with acetylsalicylic acid (aspirin) at a daily dose of =325 mg is permitted.
[9]Males and females are sterile, postmenopausal, or compliant with a highly effective contraceptive method during study participation and for 3 months following the last dose of study drug.
[10]Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose.
[11]The patient has provided signed informed consent and authorization for release of health information for research prior to any study-specific procedures and is amenable to compliance with protocol schedules and testing.
[12]Are willing to provide blood/serum/plasma and tumor tissue samples for research purpos

Exclusion Criteria

[14]Previous systemic therapy for locally advanced or metastatic disease is not allowed. Transarterial chemoembolization (TACE) or radiotherapy, including use of radioactive beads, is not allowed unless otherwise addressed in the Exclusion Criterion 18. See protocol for previous allowed treatments:
[15]Have a history of or have current hepatic encephalopathy of any grade, or ascites of Grade >1, or cirrhosis with Child-Pugh Stage B or higher.
[16]Have ongoing or recent (=6 months) hepatorenal syndrome
[17]Have had a major surgical procedure or significant traumatic injury including non-healing wound, peptic ulcer, or bone fracture =28 days prior to randomization, or anticipate having a major surgical procedure during the course of the study. Randomization should only occur after complete wound healing. Subcutaneous venous access device placement should not be considered a significant surgery, but should be placed greater than 7 days prior to randomization.
[18]Have had radiation to any site (for example, bone) within 14 days prior to randomization. Palliative radiation to symptomatic metastatic sites (for example, bone) is permitted, provided it is performed >14 days prior to randomization. If any tumor lesion is administered radiotherapy, then it cannot be considered for response assessment.
[19]Has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients without history of central nervous system (CNS) metastases is not required. However, patients with findings consistent with CNS malignancy or metastasis should be evaluated fully before study participation.
[20]Have had any previous systemic therapy with VEGF inhibitors or VEGF-Receptor inhibitors (including investigational agents).
[21]Are receiving therapeutic dose anticoagulation with warfarin, low-molecular-weight heparin, or similar agents (see also Inclusion Criterion 8d).
[22]Are receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs: for example, indomethacin, ibuprofen, naproxen, or similar agents) or other anti-platelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 mg/day is permitted
[23]Symptomatic congestive heart failure (New York Heart Association III-IV are excluded, Class I and II are eligible), unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia.
[24]Within 6 months prior to randomization, have had any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
[25]Have an uncontrolled arterial hypertension with systolic blood pressure =150 or diastolic blood pressure =90 mm Hg despite standard medical management.
[26]Have a previous malignancy within 5 years of study entry or a concurrent malignancy. Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and whose likelihood of recurrence is very low, as judged by the Lilly CRP/CRS in consultation with the treating investigator, are eligible for this study. The approval by the CRP/CRS of such patients is required before these patients may be enrolled.
[28]Have a history of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.
[29]Have a known allergy or hypersensitivity reaction to any of the treatment components.
[30]Have a history of unc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified