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A Study of Ramucirumab (IMC-1121B) With Paclitaxel and Carboplatin in Non-small Cell Lung Cancer

Primary Purpose

Non Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ramucirumab
Paclitaxel
Carboplatin
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Non Small Cell Lung Cancer, Lung, NSCLC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed NSCLC
  • Advanced NSCLC
  • Measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST 1.0])
  • Eastern Cooperative Oncology Group (ECOG) Performance Status is ≤ 1
  • Age ≥ 18 years
  • Adequate hematologic function = an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/microliter (μL)
  • Adequate hepatic function = a total bilirubin ≤ 1.5 mg/dL transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN)
  • Adequate renal function serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) > 60 mL/minute, and urine dipstick for protein < 1+ (ie, either 0 or trace)
  • Adequate coagulation function, INR ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN
  • Adequate contraception
  • Signed informed consent

Exclusion Criteria:

  • Untreated CNS metastases
  • Prior bevacizumab therapy
  • Radiologically documented evidence of major blood vessel invasion or encasement by cancer
  • Prior systemic chemotherapy for Stage IIIB/IV NSCLC
  • Prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior
  • Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix
  • Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
  • Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Uncontrolled thrombotic or hemorrhagic disorders
  • Poorly-controlled hypertension
  • Chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
  • History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon)
  • Serious non-healing wound, ulcer, or bone fracture
  • Undergone major surgery or subcutaneous venous access device placement. Post-operative bleeding complications or wound complications from a surgical procedures performed in the last 2 months
  • Elective or a planned major surgery to be performed during the course of the trial
  • Peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0])
  • If female, is pregnant or lactating
  • Radiographic evidence of intratumor cavitation
  • Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry

Sites / Locations

  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ramucirumab + paclitaxel + carboplatin

Arm Description

Participants will receive ramucirumab in combination with paclitaxel and carboplatin until disease progression, the development of an unacceptable toxicity, or other withdrawal criteria, for up to six cycles (3 weeks per cycle). In the absence of any withdrawal criteria, participants will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit upon review every 6 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Are Progression-free (PFS) at 6 Months
Data presented are the percentage of participants without disease progression or death at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progressive disease was defined as having at least a 20% increase in sum of longest diameter of target lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.

Secondary Outcome Measures

Summary of Participants Reporting Adverse Events
Data presented are the number of participants who experienced ramucirumab related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of ramucirumab treatment, and any TEAE leading to dose modification ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])
Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.
Duration of Response
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression, initiation of additional antitumor therapy is first reported, or death as a result of any cause. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
Overall Survival (OS) at 1 Year
Data presented are the percentage of participants surviving at least 12 months after first dose of study medication.
Progression-free Survival (PFS)
Defined as the time from date of first dose of study medication to the first documented disease progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.0), initiation of additional antitumor therapy was first reported or death due to any cause. Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow-up before documented progression or death were censored at date of last tumor assessment. Participants who started new therapeutic anticancer treatment prior to documented progression or death were censored at date of last tumor assessment prior to new therapeutic anticancer therapy.
Overall Survival (OS)
Overall survival is defined as the time from the first dose of study medication to the date of death from any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the patient was known to be alive.
Serum Anti-Ramucirumab Antibody Assessment
The number of participants who developed treatment emergent antibody responses to ramucirumab after baseline.
Maximum Concentration of Ramucirumab (Cmax)

Full Information

First Posted
August 13, 2008
Last Updated
December 17, 2014
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00735696
Brief Title
A Study of Ramucirumab (IMC-1121B) With Paclitaxel and Carboplatin in Non-small Cell Lung Cancer
Official Title
A Phase 2, Open-label Study of IMC-1121B in Combination With Paclitaxel and Carboplatin as First-line Therapy in Patients With Stage IIIB/IV Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the progression-free survival (PFS) rate at 6 months of ramucirumab administered in combination with paclitaxel and carboplatin as first-line therapy for Stage IIIB or IV non-small cell lung cancer
Detailed Description
Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. The advanced stages are associated with poor survival rates, a median survival rate of approximately 3.9 months if left untreated. Angiogenesis is a process for wound healing and restoring blood flow to tissues after injury. It is the physiological process involving the growth of new blood vessels from pre-existing vessels. Angiogenesis may be promoted by growth factors and in diseases such as cancer, where growth factors are over expressed, the body loses the ability to maintain a balanced angiogenesis. This may embellish the existing supplies of blood; potentially increasing the delivery of oxygen and nutrients supplies for cancer growth and survival. Ramucirumab is an angiogenesis inhibitor; and is believed to block the promotion of the growth factor to form new blood vessels, thus reducing the blood supply to the cancer cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
Non Small Cell Lung Cancer, Lung, NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ramucirumab + paclitaxel + carboplatin
Arm Type
Experimental
Arm Description
Participants will receive ramucirumab in combination with paclitaxel and carboplatin until disease progression, the development of an unacceptable toxicity, or other withdrawal criteria, for up to six cycles (3 weeks per cycle). In the absence of any withdrawal criteria, participants will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit upon review every 6 weeks.
Intervention Type
Biological
Intervention Name(s)
Ramucirumab
Other Intervention Name(s)
IMC-1121B, LY3009806
Intervention Description
10 milligrams per kilogram (mg/kg), intravenous (IV) infusion, on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
200 milligrams per meter squared (mg/m^2), administered intravenously (IV) following the ramucirumab infusion, on day 1 of each 21-day cycle, for up to six cycles.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Administered after paclitaxel, as an intravenous infusion (IV), over 30 minutes on day 1 of each 21-day cycle, for up to six cycles. The dose to be administered is calculated based on the participant's actual body weight at time of treatment and the area under the curve (AUC) dosing. The target AUC for carboplatin treatment is AUC=6.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Are Progression-free (PFS) at 6 Months
Description
Data presented are the percentage of participants without disease progression or death at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progressive disease was defined as having at least a 20% increase in sum of longest diameter of target lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Summary of Participants Reporting Adverse Events
Description
Data presented are the number of participants who experienced ramucirumab related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of ramucirumab treatment, and any TEAE leading to dose modification ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section.
Time Frame
Baseline up to 32.5 months
Title
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])
Description
Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.
Time Frame
First dose to measured progressive disease or death due to any cause up to 32.5 months
Title
Duration of Response
Description
The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression, initiation of additional antitumor therapy is first reported, or death as a result of any cause. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
Time Frame
First dose up to 32.5 months
Title
Overall Survival (OS) at 1 Year
Description
Data presented are the percentage of participants surviving at least 12 months after first dose of study medication.
Time Frame
First dose to 1 year
Title
Progression-free Survival (PFS)
Description
Defined as the time from date of first dose of study medication to the first documented disease progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.0), initiation of additional antitumor therapy was first reported or death due to any cause. Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow-up before documented progression or death were censored at date of last tumor assessment. Participants who started new therapeutic anticancer treatment prior to documented progression or death were censored at date of last tumor assessment prior to new therapeutic anticancer therapy.
Time Frame
First dose to measured progressive disease or death due to any cause, up to 32.5 months
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from the first dose of study medication to the date of death from any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the patient was known to be alive.
Time Frame
First dose to death due to any cause, up to 32.5 months
Title
Serum Anti-Ramucirumab Antibody Assessment
Description
The number of participants who developed treatment emergent antibody responses to ramucirumab after baseline.
Time Frame
Week 15 (Cycle 5)
Title
Maximum Concentration of Ramucirumab (Cmax)
Time Frame
Week 18 (Cycle 6), at 1-Hour Post End of Infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed NSCLC Advanced NSCLC Measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST 1.0]) Eastern Cooperative Oncology Group (ECOG) Performance Status is ≤ 1 Age ≥ 18 years Adequate hematologic function = an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/microliter (μL) Adequate hepatic function = a total bilirubin ≤ 1.5 mg/dL transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN) Adequate renal function serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) > 60 mL/minute, and urine dipstick for protein < 1+ (ie, either 0 or trace) Adequate coagulation function, INR ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN Adequate contraception Signed informed consent Exclusion Criteria: Untreated CNS metastases Prior bevacizumab therapy Radiologically documented evidence of major blood vessel invasion or encasement by cancer Prior systemic chemotherapy for Stage IIIB/IV NSCLC Prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Uncontrolled thrombotic or hemorrhagic disorders Poorly-controlled hypertension Chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) Serious non-healing wound, ulcer, or bone fracture Undergone major surgery or subcutaneous venous access device placement. Post-operative bleeding complications or wound complications from a surgical procedures performed in the last 2 months Elective or a planned major surgery to be performed during the course of the trial Peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0]) If female, is pregnant or lactating Radiographic evidence of intratumor cavitation Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
ImClone Investigational Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
ImClone Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
ImClone Investigational Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
ImClone Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
ImClone Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
ImClone Investigational Site
City
Cambridge
Country
United Kingdom
Facility Name
ImClone Investigational Site
City
London
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study of Ramucirumab (IMC-1121B) With Paclitaxel and Carboplatin in Non-small Cell Lung Cancer

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