Ramucirumab/Merestinib + Chemotherapy for Biliary Tract Cancer

Recruiting at 161 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Hepatic encephalopathy, Cirrhosis, Brain metastases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: 24 weeks

309 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since previous systemic therapy for advanced or metastatic disease is not allowed, you may need to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Ramucirumab/Merestinib with chemotherapy for biliary tract cancer?

A study evaluated the addition of ramucirumab or merestinib to standard chemotherapy for advanced biliary tract cancer, aiming to assess their effectiveness and safety. Another study found that ramucirumab, which targets a protein involved in blood vessel growth in tumors, was investigated for its potential benefits in advanced biliary tract cancer previously treated with chemotherapy. ^{1 2 3 4 5}

Is the combination of Ramucirumab/Merestinib with chemotherapy safe for humans?

The combination of Ramucirumab with chemotherapy has been studied in patients with advanced biliary tract cancer and showed no unexpected safety issues, aligning with previous safety reports for other conditions. ^{1 3 5 6 7}

How is the drug combination of Ramucirumab and Merestinib with chemotherapy unique for treating biliary tract cancer?

This treatment is unique because it combines Ramucirumab, which targets VEGFR-2 to block blood vessel growth in tumors, with Merestinib and standard chemotherapy, potentially offering a new approach for advanced biliary tract cancer, which has limited treatment options. ^{1 2 4 5 6}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for adults with advanced or metastatic biliary tract cancer who haven't had previous systemic therapy for their condition. They must be relatively healthy and active (with good performance status), have measurable disease, provide tissue samples, have proper organ function and biliary drainage, and use effective contraception if of childbearing potential.

Inclusion Criteria

My cancer is a type of biliary tract cancer that cannot be surgically removed.

Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST)

My organs are functioning well.

Exclusion Criteria

I have had cancer or have another cancer besides the one being studied.

I expect to undergo a major surgery during the study.

I do not have severe health issues unrelated to my cancer that could risk my life.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ramucirumab or merestinib or placebo plus cisplatin and gemcitabine for up to 8 cycles

24 weeks

Visits every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Treatment Details

Interventions

• Merestinib
• Ramucirumab

Trial Overview The study tests the effectiveness and safety of two drugs: Ramucirumab or Merestinib, each combined with Cisplatin and Gemcitabine chemotherapy. Participants will also receive either a placebo pill or IV to compare against these treatments.

Participant Groups

Group I: 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine Experimental Treatment 3 Interventions

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).

Group II: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine Experimental Treatment 3 Interventions

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).

Group III: Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine Placebo Group 3 Interventions

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).

Group IV: Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine Placebo Group 3 Interventions

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).

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

In a study involving 117 patients with advanced biliary tract cancer, rising levels of circulating VEGFA were linked to worse progression-free survival (PFS) and overall survival (OS) in those treated with cisplatin/gemcitabine, but this negative effect was reduced in patients receiving cediranib.

The study found that increases in circulating CK18 and VEGFR2 levels were associated with poorer outcomes, suggesting these markers could help predict patient prognosis and treatment response, highlighting the potential for using minimally invasive biomarkers in managing advanced biliary tract cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. Backen, AC., Lopes, A., Wasan, H., et al.[2022]

In a phase I/II trial involving 41 patients with untreated advanced biliary tract cancer, the maximum tolerated dose (MTD) of binimetinib was established at 45 mg twice daily when combined with gemcitabine and cisplatin, showing a median overall survival of 13.3 months.

Despite the treatment regimen, the combination of binimetinib with chemotherapy did not improve progression-free survival (PFS) or response rate (RR), suggesting that molecular profiling may be necessary to identify patients who could benefit from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers. Lowery, MA., Bradley, M., Chou, JF., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

New Treatment Options for Advanced Biliary Tract Cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II Study of Ramucirumab in Advanced Biliary Tract Cancer Previously Treated By Gemcitabine-Based Chemotherapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Ramucirumab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer: Nonrandomized, Open-Label, Phase I Trial (JVDF). [2023]