A Study of Ramucirumab (LY3009806) in Combination With Paclitaxel in Participants With Gastric Cancer

• ClinicalTrials.gov Identifier: NCT02514551
• Recruitment Status: Completed
• First Posted: August 3, 2015
• Results First Posted: December 19, 2018
• Last Update Posted: March 6, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The main purpose of this study is to evaluate the efficacy of an alternative dose of ramucirumab in combination with paclitaxel in participants with second-line metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma (GEJ).

Condition or disease	Intervention/treatment	Phase
Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma	Drug: Ramucirumab; Drug: Paclitaxel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 245 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase 2 Trial Evaluating Alternative Ramucirumab Doses in Combination With Paclitaxel in Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma
• Actual Study Start Date: October 12, 2015
• Actual Primary Completion Date: October 27, 2017
• Actual Study Completion Date: December 28, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel; 12mg/kg ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B; Cyramza; Drug: Paclitaxel; Administered IV
Active Comparator: 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel; 8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15.	Drug: Ramucirumab; Administered IV; Other Names: LY3009806; IMC-1121B; Cyramza; Drug: Paclitaxel; Administered IV

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ [ Time Frame: Randomization to Objective Progressive Disease or Death (Up To 21 Months) ]
   PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(ast) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with in-complete baseline disease ast PFS time was censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease ast.

Secondary Outcome Measures :

1. Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ [ Time Frame: Randomization to Objective Progressive Disease or Death (Up To 21 Months) ]
   PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(ast) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with in-complete baseline disease ast PFS time was censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease ast.
2. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel [ Time Frame: Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D29: 3 days PTI; C2 D43: 3 days PTI,1 to 1.5 hrs after EOI; C3 D57 and 71: 3 days PTI; C4 D85: 3 days PTI and 1 to 1.5 hrs after EOI ]
   Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel
3. Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) [ Time Frame: Baseline to Objective Progressive Disease (Up To 21 Months) ]
   ORR was defined as the percentage of participants achieving a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.Progressive Disease(PD)is at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.NonTarget PD is unequivocal progression of existing nontarget lesions.The appearance of 1 or more new lesions is also considered PD.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
4. Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)] [ Time Frame: Baseline to Objective Progressive Disease (Up To 21 Months) ]
   DCR is defined as the percentage of participants CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study. In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions.
5. Number of Participants With Anti-Ramucirumab Antibodies [ Time Frame: Cycle 1 Predose through Follow-up (Up To 24 Months) ]
   Participants who had anti-ramucirumab antibodies at postbaseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The participant has a diagnosis of gastric or GEJ adenocarcinoma.
• The participant has disease progression during or within 4 months after last dose of first-line chemotherapy or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.
• The participant received combination chemotherapy, which must include a platinum and/or a fluoropyrimidine and must not include a taxane or antiangiogenic agent.
• The disease is evaluable by imaging per Response Evaluation Criteria in Solid Tumors 1.1.
• The participant has an Eastern Cooperative Oncology Group performance status of 0 or 1.

• The participant has adequate organ function:

  • Total bilirubin ≤1.5 × the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN.
  • Serum creatinine ≤1.5 × ULN or calculated creatinine clearance ≥50 milliliters/minute.
  • Urinary protein is <2+.
  • Absolute neutrophil count ≥1.5 × 10^9/liter (L), platelets ≥100 × 10^9/L, and hemoglobin ≥9 grams/deciliter (5.58 millimoles/L).
  • International normalized ratio ≤1.5 × ULN and partial thromboplastin time ≤5 seconds above ULN.
• The participant has an estimated life expectancy of minimum 12 weeks.
• The participant has resolution to Grade 1 or less by Common Terminology Criteria for Adverse Events Version 4.0, of all clinically significant toxic effects of previous therapy.
• The participant, if male, is sterile or agrees to use a reliable method of birth control.
• The participant, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control.
• The participant, if female and of child-bearing potential, must have a negative pregnancy test.

Exclusion Criteria:

• The participant is receiving therapy with any of the following:

  • Nonsteroidal anti-inflammatory agents.
  • Other anti-platelet agents; Aspirin use at doses up to 325 milligrams (mg)/day is permitted.
• The participant received radiotherapy within 14 days prior to randomization.
• The participant received previous chemotherapy with a cumulative dose of >900 mg per meter squared (mg/m^2) of epirubicin or >400 mg/m^2 of doxorubicin.
• The participant has documented brain metastases or leptomeningeal disease.
• The participant has a significant bleeding disorder or vasculitis.
• The participant experienced any arterial thromboembolic event within 6 months.
• The participant has symptomatic congestive heart failure or symptomatic cardiac arrhythmia.
• The participant has uncontrolled hypertension, despite antihypertensive intervention.
• The participant underwent major surgery within 28 days.
• The participant has a history of gastrointestinal perforation or fistula within 6 months.
• The participant has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months.
• The participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant.

• The participant has either of the following:

  • Child-pugh B or C cirrhosis.

• The participant has a serious illness or medical condition including:

  • Human immunodeficiency virus infection.

• The participant has a concurrent active malignancy other than the following:

  • Nonmelanomatous skin cancer.
  • In situ carcinoma of the cervix or other noninvasive carcinoma or in situ neoplasm.
• The participant has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture.
• The participant experienced any Grade 3 or 4 venous thromboembolic event that is not adequately treated.

Contacts and Locations

  Show 52 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: 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); Eli Lilly and Company

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Study Protocol  [PDF] May 7, 2015

Statistical Analysis Plan  [PDF] November 15, 2017

More Information

Additional Information:

Click here for more information about this study: A Study of Ramucirumab (LY3009806) in Combination With Paclitaxel in Participants With Gastric Cancer 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02514551 History of Changes
• Other Study ID Numbers: 15541; I4T-MC-JVCZ ( Other Identifier: Eli Lilly and Company ); 2014-005067-32 ( EudraCT Number )
• First Posted: August 3, 2015
• Results First Posted: December 19, 2018
• Last Update Posted: March 6, 2019
• Last Verified: March 1, 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Keywords provided by Eli Lilly and Company:

stomach cancer

Additional relevant MeSH terms:

Adenocarcinoma; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Paclitaxel; Albumin-Bound Paclitaxel; Ramucirumab; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action