Clinical trial NCT00735696: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: Non Small Cell Lung Cancer
Lung
NSCLC
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-08-15
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants Who Are Progression-free (PFS) at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Summary of Participants Reporting Adverse Events
timeFrame: Baseline up to 32.5 months
measure: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])
timeFrame: First dose to measured progressive disease or death due to any cause up to 32.5 months
measure: Duration of Response
timeFrame: First dose up to 32.5 months
measure: Overall Survival (OS) at 1 Year
timeFrame: First dose to 1 year
measure: Progression-free Survival (PFS)
timeFrame: First dose to measured progressive disease or death due to any cause, up to 32.5 months
measure: Overall Survival (OS)
timeFrame: First dose to death due to any cause, up to 32.5 months
measure: Serum Anti-Ramucirumab Antibody Assessment
timeFrame: Week 15 (Cycle 5)
measure: Maximum Concentration of Ramucirumab (Cmax)
timeFrame: Week 18 (Cycle 6), at 1-Hour Post End of Infusion
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: ImClone Investigational Site
state: California
city: San Francisco
country: United States
facility: ImClone Investigational Site
state: California
city: Aurora
country: United States
facility: ImClone Investigational Site
state: Colorado
city: Bronx
country: United States
facility: ImClone Investigational Site
state: New York
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: San Antonio
country: United States
facility: ImClone Investigational Site
state: Texas
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
city: Cambridge
country: United Kingdom
facility: ImClone Investigational Site
city: London
country: United Kingdom
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: