A Study of Ramucirumab 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: August 16, 2013
Last verified: August 2013
  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: Allocation: Non-Randomized
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:
  • Proportion of Participants Who are Progression-free (PFS) at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The 6-month progression-free survival (PFS) rate is defined as the proportion of participants that are alive and progression-free 6 months after randomization.


Secondary Outcome Measures:
  • Summary of Participants Reporting Adverse Events [ Time Frame: up to 36 months ] [ Designated as safety issue: Yes ]
  • Proportion of Participants with Objective Response (Objective Response Rate or ORR) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    The objective response rate (ORR) is the proportion of participants achieving a best overall response of partial or complete response (PR + CR).

  • Duration of Response [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Duration of response is the interval from date of initial documented response (complete response or partial response) to the first documented date of disease progression or death.

  • Overall Survival (OS) at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Number of participants who are alive at one year.

  • Progression-free Survival (PFS) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever is first.

  • Overall Survival (OS) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from the date of randomization to the date of death from any cause.

  • Serum Anti-Ramucirumab Antibody Assessment [ Time Frame: up to Week 15 ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) (week 18, cycle 6) [ Time Frame: Week 18 ] [ 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

Patients 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, patients will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit review every 6 weeks.

Biological: Ramucirumab
Intravenous (I.V.) infusion at 10mg/kg on day 1 of each 21-day cycle. Each infusion lasts one hour.
Other Name: 1121B
Drug: Paclitaxel
Paclitaxel 200 mg/m2 is administered intravenously over 3 hours following the ramucirumab infusion on day 1 for up to six 21-day cycles.
Drug: Carboplatin
Carboplatin is administered after paclitaxel as an intravenous infusion over 30 minutes on day 1 for up to six 21-day cycles. The dose of carboplatin to be administered is calculated based on the patient's actual body weight at each treatment visit 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; and the advanced stages are associated with poor survival rates with untreated patients having a median survival rate of approximately 3.9 months.

Angiogenesis is a process that occurs in the health body for wound healing and restoring blood flow to tissues after injury. It is the physiological proves 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 forming new blood vessels, thus reducing the amount of blood supplies to the cancer cells.

In this study, 40 adult patients with NSCLC will be evaluated t=for progression-free survival at 6 months of ramucirumab administration

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed NSCLC
  2. Advanced NSCLC
  3. Measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST])
  4. ECOG is ≤ 1
  5. Age ≥ 18 years
  6. Adequate hematologic function = an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/μL
  7. Adequate hepatic function = a total bilirubin ≤ 1.5 mg/dL transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN)
  8. 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)
  9. Adequate coagulation function, INR ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN
  10. Adequate contraception
  11. Signed informed consent

Exclusion Criteria:

  1. Untreated CNS metastases
  2. Prior bevacizumab therapy
  3. Radiologically documented evidence of major blood vessel invasion or encasement by cancer
  4. Prior systemic chemotherapy for Stage IIIB/IV NSCLC
  5. Prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior
  6. Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix
  7. Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization,or targeted therapy
  8. 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
  9. Uncontrolled thrombotic or hemorrhagic disorders
  10. Poorly-controlled hypertension
  11. Chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
  12. History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon)
  13. Serious non-healing wound, ulcer, or bone fracture
  14. 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
  15. Elective or a planned major surgery to be performed during the course of the trial
  16. Peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0])
  17. If female, is pregnant or lactating
  18. Radiographic evidence of intratumor cavitation
  19. 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
Last Updated: August 16, 2013
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
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 14, 2014