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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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00326599
First received: May 16, 2006
Last updated: February 16, 2017
Last verified: February 2017
May 16, 2006
February 16, 2017
June 2007
April 2009   (Final data collection date for primary outcome measure)
Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II Patients Only) [ Time Frame: 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
Not Provided
Complete list of historical versions of study NCT00326599 on ClinicalTrials.gov Archive Site
  • Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only) [ Time Frame: 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.

  • Progression-free Survival (Phase II Patients Only) [ Time Frame: 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.
  • Time to Treatment Failure (Phase II Patients Only) [ Time Frame: 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.
  • Overall Survival at 1 Year After Randomization (Phase II Patients Only) [ Time Frame: 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.
  • Overall Survival (Phase II Patients Only) [ Time Frame: 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.
  • Dose Limiting Toxicity (DLT) (Lead-in Phase Arm I Patients Only) [ Time Frame: 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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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
A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Lung Cancer
  • Drug: carboplatin
    Given IV
  • Drug: cediranib maleate
    Given orally
  • Drug: gemcitabine hydrochloride
    Given IV
  • Experimental: 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.
    Interventions:
    • Drug: carboplatin
    • Drug: cediranib maleate
    • Drug: gemcitabine hydrochloride
  • Active Comparator: 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.
    Interventions:
    • Drug: carboplatin
    • Drug: gemcitabine hydrochloride

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
101
February 2010
April 2009   (Final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

    • Squamous cell histology allowed
    • No mixed histology with small cell component
  • Stage IIIB (with pleural effusion) or stage IV disease

    • Presence of peritoneal or pericardial effusion alone in the absence of cytologic evidence is not allowed
  • Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan

    • If the only site of measurable disease was previously irradiated, progressive disease must be evident
  • Ineligible for bevacizumab therapy
  • No symptomatic, untreated, or uncontrolled CNS metastases

    • CNS metastases treated with whole-brain radiation (WBRT) allowed 4 weeks after completion of WBRT

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • ALT and AST ≤ 3 times ULN (5 times ULN if liver involvement)
  • Alkaline phosphatase ≤ 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective nonhormonal contraception
  • No proteinuria ≥ 1+
  • No uncontrolled blood pressure (BP), defined as systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg in spite of adequate antihypertensive therapy
  • No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of AZD2171 (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection)
  • No seizure disorder
  • No significant traumatic injury within 4 weeks prior to study entry
  • No second primary malignancy except any of the following:

    • Carcinoma in situ of the cervix
    • Nonmelanoma skin cancer
    • Prior malignancy diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
    • History of low-grade (Gleason score ≤ 6) localized prostate cancer even if diagnosed < 5 years prior to registration
    • Treated stage I breast cancer ≤ 5 years prior to registration
  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Significant pulmonary symptoms at baseline due to disease
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would limit compliance with study requirements
    • Baseline hemoptysis
    • Cavitating lesions
  • No QTc prolongation > 500 msec or other significant ECG abnormality within the past 14 days
  • No New York Heart Association class III or IV disease

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy for advanced lung cancer

    • Neoadjuvant or adjuvant therapy for lung cancer within the past 12 months allowed
  • More than 12 months since prior immunotherapy and biologic therapy
  • More than 4 weeks since prior radiotherapy (2 weeks for palliative radiotherapy to skeletal metastases)
  • At least 2 weeks since prior WBRT
  • No radiotherapy to ≥ 25% of bone marrow
  • No major surgery (i.e., laparotomy) or open biopsy within 4 weeks prior to study entry (2 weeks for minor surgery)

    • Insertion of a vascular access device not considered major or minor surgery
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent grapefruit or grapefruit juice during AZD2171 treatment
  • No concurrent drugs or biologics with proarrhythmic potential
  • Concurrent palliative radiotherapy to nontarget sites (i.e., painful pre-existing bony metastasis) allowed with AZD2171 (chemotherapy is held until completion of radiotherapy)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00326599
NCCTG-N0528
NCI-2012-02694 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000468945 ( Registry Identifier: PDQ (Physician Data Query) )
No
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Alex A. Adjei, MD, PhD Roswell Park Cancer Institute
Alliance for Clinical Trials in Oncology
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP