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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00735696
First received: August 13, 2008
Last updated: December 17, 2014
Last verified: December 2014
  Purpose

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


Condition Intervention Phase
Non Small Cell Lung Cancer
Biological: Ramucirumab
Drug: Paclitaxel
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percentage of Participants Who Are Progression-free (PFS) at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to 32.5 months ] [ Designated as safety issue: Yes ]
    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]) [ Time Frame: First dose to measured progressive disease or death due to any cause up to 32.5 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: First dose up to 32.5 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: First dose to 1 year ] [ Designated as safety issue: No ]
    Data presented are the percentage of participants surviving at least 12 months after first dose of study medication.

  • Progression-free Survival (PFS) [ Time Frame: First dose to measured progressive disease or death due to any cause, up to 32.5 months ] [ Designated as safety issue: No ]

    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) [ Time Frame: First dose to death due to any cause, up to 32.5 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 15 (Cycle 5) ] [ Designated as safety issue: Yes ]
    The number of participants who developed treatment emergent antibody responses to ramucirumab after baseline.

  • Maximum Concentration of Ramucirumab (Cmax) [ Time Frame: Week 18 (Cycle 6), at 1-Hour Post End of Infusion ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: January 2009
Study Completion Date: January 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ramucirumab + paclitaxel + carboplatin

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.

Biological: Ramucirumab
10 milligrams per kilogram (mg/kg), intravenous (IV) infusion, on Day 1 of each 21-day cycle.
Other Names:
  • IMC-1121B
  • LY3009806
Drug: Paclitaxel
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.
Drug: Carboplatin
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00735696

Locations
United States, California
ImClone Investigational Site
Beverly Hills, California, United States, 90211
ImClone Investigational Site
San Francisco, California, United States, 94143
United States, Colorado
ImClone Investigational Site
Aurora, Colorado, United States, 80045
United States, New York
ImClone Investigational Site
Bronx, New York, United States, 10467
ImClone Investigational Site
New York, New York, United States, 10016
United States, Texas
ImClone Investigational Site
San Antonio, Texas, United States, 78229
United States, Washington
ImClone Investigational Site
Seattle, Washington, United States, 98104
United Kingdom
ImClone Investigational Site
Cambridge, United Kingdom
ImClone Investigational Site
London, United Kingdom
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00735696     History of Changes
Other Study ID Numbers: 13914, 2007-006715-22, CP12-0708, I4T-IE-JVBJ
Study First Received: August 13, 2008
Results First Received: December 17, 2014
Last Updated: December 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Eli Lilly and Company:
Non Small Cell Lung Cancer
Lung
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on May 29, 2015