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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02514551
Recruitment Status : Completed
First Posted : August 3, 2015
Results First Posted : December 19, 2018
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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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
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (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
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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 incomplete baseline disease had PFS time 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 incomplete baseline disease had PFS time 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 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 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 who achieved 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.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 who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (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. DCR=CR+PR+SD/total number of participants*100.

  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
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Information from the National Library of Medicine

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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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02514551


Locations
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Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
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Additional Information:

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02514551    
Other Study ID Numbers: 15541
I4T-MC-JVCZ ( Other Identifier: Eli Lilly and Company )
2014-005067-32 ( EudraCT Number )
First Posted: August 3, 2015    Key Record Dates
Results First Posted: December 19, 2018
Last Update Posted: June 17, 2020
Last Verified: June 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Keywords provided by Eli Lilly and Company:
stomach cancer
Additional relevant MeSH terms:
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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
Ramucirumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action