A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

Lilly

Status and phase: Active, not recruiting; Phase 2

Conditions: Advanced Cancer; Metastatic Cancer; Biliary Tract Cancer

Treatments: Drug: Ramucirumab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebo Oral; Drug: Placebo IV; Drug: Merestinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02711553

I3O-MC-JSBF (Other Identifier)

2015-004699-31 (EudraCT Number)

16329 (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab or merestinib or placebo plus cisplatin and gemcitabine in participants with advanced or metastatic biliary tract cancer.

Enrollment: 309 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
• 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) .
• Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
• Have adequate biliary drainage.
• Have adequate organ function.
• Males and females are sterile, postmenopausal, or compliant with a highly effective contraceptive method.
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose.
• Are willing to provide blood/serum/plasma and tumor tissue samples for research purposes. Submission of blood/serum/plasma and tumor tissue samples is mandatory for participation in this study, unless restricted per local regulations.

Exclusion criteria

• Previous systemic therapy for locally advanced or metastatic disease is not allowed.
• 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.
• Have ongoing or recent (≤6 months) hepatorenal syndrome.
• Have had a major surgical procedure or significant traumatic injury including nonhealing wound, peptic ulcer, or bone fracture ≤28 days prior to randomization.
• Anticipate having a major surgical procedure during the course of the study.
• Has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• Within 6 months prior to randomization, have had any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
• Have an uncontrolled arterial hypertension with systolic blood pressure ≥150 or diastolic blood pressure ≥90 millimeters of mercury (mm Hg) despite standard medical management.
• Have a previous malignancy within 5 years of study entry or a concurrent malignancy.
• Have a history of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.
• Have a known allergy or hypersensitivity reaction to any of the treatment components.
• Have a history of uncontrolled hereditary or acquired thrombotic disorder.
• Have uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain.
• Have mixed hepatocellular biliary tract cancer histology.
• Have a corrected QT interval >470 milliseconds as calculated by the Fridericia equation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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309 participants in 4 patient groups, including a placebo group

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Experimental group

Description:

Participants received 8 mg/kg ramucirumab plus 25 mg/square meter (mg/m²) cisplatin and 1000 mg/m² gemcitabine intravenously (IV) on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Drug: Ramucirumab

Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo Comparator group

Description:

Participants received placebo (indistinguishable and equivalent volume to ramucirumab) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Treatment:

Drug: Placebo IV

Drug: Cisplatin

Drug: Gemcitabine

80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Experimental group

Description:

Participants received 80 mg merestinib orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for merestinib therapy).

Treatment:

Drug: Merestinib

Drug: Cisplatin

Drug: Gemcitabine

Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo Comparator group

Description:

Participants received placebo (indistinguishable to merestinib) orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days. Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Treatment:

Drug: Placebo Oral

Drug: Cisplatin

Drug: Gemcitabine