Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT00326599
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving gemcitabine and carboplatin together with AZD2171 may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying how well giving gemcitabine and carboplatin together with AZD2171 works compared to giving gemcitabine and carboplatin without AZD2171 as first-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
- Detailed Description
OBJECTIVES:
Primary
* Assess the objective tumor response rate in patients with stage IIIB or IV non-small cell lung cancer treated with gemcitabine hydrochloride, carboplatin, and AZD2171 as first-line therapy.
Secondary
* Compare the proportion of patients who are progression-free at 6 months after treatment with gemcitabine hydrochloride and carboplatin with vs without AZD2171.
* Compare the duration of response for responding patients treated with these regimens.
* Compare the time-to-progression and time-to-treatment failure.
* Compare the 1-year overall survival.
* Compare the clinical toxicities.
* Assess the safety and tolerability of these regimens in these patients.
Tertiary
* Collect blood and tumor specimens for future evaluation of pharmacogenetic and proteomic markers of tumor response and toxicity to therapy with these agents.
* Bank paraffin-embedded tissue blocks/slides and blood samples for future histochemistry evaluation and DNA extraction.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant therapy (yes vs no) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive gemcitabine and carboplatin as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for pharmacologic correlative studies.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 102 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I cediranib maleate Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity. Arm II gemcitabine hydrochloride Patients receive gemcitabine and carboplatin as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm I gemcitabine hydrochloride Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity. Arm I carboplatin Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral AZD2171 once daily on days 1-21. Treatment repeats every 21 days for up to 6 courses. Patients achieving stable disease, partial response, or complete response after 6 courses of therapy receive AZD2171 alone as above. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity. Arm II carboplatin Patients receive gemcitabine and carboplatin as in arm I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II Patients Only) Up to 5 years A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart.
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:
* Complete Response (CR): disappearance of all target lesions;
* Partial Response (PR) 30% decrease in sum of longest diameter of target lesions
- Secondary Outcome Measures
Name Time Method Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only) 6 months Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.Overall Survival (Phase II Patients Only) Up to 5 years Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up.
Progression-free Survival (Phase II Patients Only) Up to 5 years Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression.
Overall Survival at 1 Year After Randomization (Phase II Patients Only) 1 year Overall survival was defined as the time from study enrollment to the time of death from any cause. A patient is classified as a success if alive at 1 year.
Time to Treatment Failure (Phase II Patients Only) Up to 15 months Time to treatment failure was defined to be the time from date of registration to the date at which the patient was removed from the treatment due to progression, toxicity, refusal or death from any cause.
Dose Limiting Toxicity (DLT) (Lead-in Phase Arm I Patients Only) Cycle 1 (up to 3 weeks) DLT was defined as an adverse event occurring in cycle 1 only, at least possibly attributed to the study treatment and meeting the following criteria: 1) Grade 4 absolute neutrophil count (ANC) \>5 days or of any duration with fever \>38.5 degree Celsius; 2) Grade 4 platelet count; 3) Grade 3 or higher non-hematologic toxicities (for nausea, vomiting or diarrhea, grade 3 toxicities will be DLT if they occur despite maximal use of anti-emetic support or anti-diarrhea agents, respectively); 4) Cediranib dose interruption of \>14 days for drug-related toxicities.
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Trial Locations
- Locations (151)
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Graham Hospital
🇺🇸Canton, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Clinic, PC
🇺🇸Galesburg, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Scroll for more (141 remaining)Mayo Clinic Scottsdale🇺🇸Scottsdale, Arizona, United States