Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Rare Diseases

Neoplasm Metastasis

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Ramucirumab

Antimetabolites

Angiogenesis Inhibitors

Growth Inhibitors

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).

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).

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).

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).

Merestinib

Placebo Oral

Placebo IV

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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.

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

Randomized, Double-Blind, Phase 2 Study of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine as First-Line Treatment in Patients With Advanced or Metastatic Biliary Tract Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

OS defined as the time from from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

ORR was the number of participants who achieve a best overall response of CR or PR divided by the total number of participants randomized to the corresponding treatment arm as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Disease Control Rate (DCR) was the number of participants who achieve a best overall response of CR, PR, or SD divided by the total number of participants randomized to the corresponding treatment arm as per RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

PK was determined by the minimum observed plasma concentration (Cmin). 1 Cycle (C) = 21 days (D).

PK was presented through graphical overlay comparison versus historic data. No numerical summary of data was intended or produced.

Number of participants with positive treatment emergent anti-ramucirumab antibodies (ADA) was summarized by treatment group.

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180.Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state.

EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. The second part is assessed using a VAS on which the patient rates their perceived health state, ranging from 0 millimeter (the worst health you can imagine) to 100 millimeter (the best health you can imagine).

Eli Lilly and Company

All randomized participants who received at least 1 dose of study drug.

Participants received 8 mg/kg 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 ramucirumab therapy).

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

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

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

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

Total

Age, Continuous

All randomized participants

All randomized participants who received at least 1 dose of study drug

All randomized participants and all randomized participants who received at least 1 dose of study drug to align gender specific adverse event numbers.

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Argentina

Hungary

United States

Czechia

United Kingdom

Russia

Spain

Austria

South Korea

Sweden

Turkey

Belgium

Taiwan

Denmark

Mexico

Australia

France

Germany

Region of Enrollment

Chief Medical Officer

Participants received placebo IV and placebo oral (indistinguishable and equivalent volume to ramucirumab and merestinib) 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).

Pooled Placebo

All randomized participants. Censored participants: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 29; 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 34; Pooled Placebo = 25. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Progression Free Survival (PFS)

Overall Survival (OS)

All randomized participants. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Cycle 1 Day 8 (Week 1)

Cycle 2 Day 1 (Week 3)

Cycle 3 Day 1 (Week 6)

Cycle 4 Day 1 (Week 9)

Cycle 5 Day 1 (Week 12)

Cycle 7 Day 1 (Week 18)

Cycle 9 Day 1 (Week 24)

Cycle 13 Day 1 (Week 36)

All participants who received at least one dose of study drug and had evaluable PK data. As per protocol, Cmin of merestinib was not measured.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Zero participants were analyzed as no data collected for summary analysis.

PK: Plasma Concentration of Merestinib

All randomized participants who received at least 1 dose of study drug with both baseline and at least one post baseline ADA assessments.

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

FACT-Hep

All randomized participants who received at least 1 dose of study drug with baseline and one post-baseline FACT-Hep Questionnaire.

Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)

All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for placebo oral

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