Ramucirumab/Merestinib + Chemotherapy for Biliary Tract Cancer

Not currently recruiting at 194 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of two new drugs, ramucirumab (Cyramza) and merestinib, combined with standard chemotherapy for advanced biliary tract cancer. Participants will be divided into groups to receive either the experimental drugs with chemotherapy or a placebo with chemotherapy. The goal is to determine if these new treatments can manage the cancer more effectively than standard care alone. The trial seeks individuals with advanced biliary tract cancer that cannot be surgically removed and who have not previously received systemic therapy for their advanced cancer. As a Phase 2 trial, the research focuses on measuring how well the treatment works in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using ramucirumab with pembrolizumab did not cause any unexpected safety issues for patients with advanced biliary tract cancer. Studies have identified common side effects, such as low white blood cell counts and low platelet counts, which were expected and managed. Similarly, research on merestinib indicates it is generally safe. Combining ramucirumab or merestinib with cisplatin and gemcitabine was well tolerated, with no new safety concerns. Overall, both treatments have been used in other studies and are considered safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ramucirumab and merestinib for biliary tract cancer because they offer unique ways to tackle the disease compared to standard chemotherapy. Most current treatments focus on directly killing cancer cells, often with significant side effects. Ramucirumab works differently by targeting and blocking a protein that helps tumors grow new blood vessels, essentially starving the tumor. Merestinib, on the other hand, inhibits multiple signaling pathways that cancer cells use to grow and spread, potentially offering a more comprehensive attack on the disease. These novel approaches provide hope for more effective and potentially less toxic treatment options.

What evidence suggests that this trial's treatments could be effective for biliary tract cancer?

This trial will evaluate the addition of ramucirumab or merestinib to standard chemotherapy for biliary tract cancer. Research has shown that adding ramucirumab to chemotherapy, which participants in one arm of this trial may receive, was generally well-tolerated but did not significantly extend survival time compared to a placebo. Similarly, merestinib, tested in another arm of this trial, did not slow cancer progression. Although both treatments were well-tolerated, previous studies found they did not enhance the effectiveness of standard chemotherapy. ^{2 4 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Have a corrected QT interval >470 milliseconds as calculated by the Fridericia equation.

I expect to undergo a major surgery during the study.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. tandfonline.com tandfonline.com/doi/full/10.1080/23808993.2022.2095903

Full article: Ramucirumab or merestinib in biliary tract cancer Surgical resection represents the only potentially curative treatment option for BTC patients, but even following radical surgery with curative intent, 5-year ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34592180/

Addition of ramucirumab or merestinib to standard first-line ... Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02711553

NCT02711553 | A Study of Ramucirumab (LY3009806) or ... 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204521004095

Addition of ramucirumab or merestinib to standard first-line ... Adding ramucirumab or merestinib to first-line cisplatin–gemcitabine was well tolerated, with no new safety signals, but neither improved progression-free ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/comment/eli-lilly-phase-ii-merestinib-no-pfs-improvement-in-1l-biliary-tract-cancer/

Eli Lilly's Phase II merestinib in biliary tract cancer plunges ... LoA of Eli Lilly's Phase II merestinib in 1L biliary tract cancer dropped by 2 points as of 22 February, according to GlobalData's LoA data.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30833489/

First-in-Human Phase I Study of Merestinib, an Oral ... This study demonstrates that merestinib has a tolerable safety profile and potential anticancer activity and warrants further clinical investigation.

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00409-5/abstract

Addition of ramucirumab or merestinib to standard first-line ... Adding ramucirumab or merestinib to first-line cisplatin–gemcitabine was well tolerated, with no new safety signals, but neither improved ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8495281/

Merestinib monotherapy or in combination for japanese ... Merestinib monotherapy is tolerable in Japanese patients, and its combination with cisplatin and gemcitabine is a tolerable regimen for Japanese patients with ...