Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	NCCTG-N0528 N0528, NCT00326599

Objectives

Primary

1. 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

1. Compare the proportion of patients who are progression-free at 6 months after treatment with gemcitabine hydrochloride and carboplatin with vs without AZD2171.
2. Compare the duration of response for responding patients treated with these regimens.
3. Compare the time-to-progression and time-to-treatment failure.
4. Compare the 1-year overall survival.
5. Compare the clinical toxicities.
6. Assess the safety and tolerability of these regimens in these patients.

Tertiary

1. Collect blood and tumor specimens for future evaluation of pharmacogenetic and proteomic markers of tumor response and toxicity to therapy with these agents.
2. Correlate quantitative changes in circulating endothelial cells and endothelial progenitor cells with clinical response and toxicity.

Entry Criteria

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

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)

Patient Characteristics:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

A total of 102 patients will be accrued for this study.

Outcomes

Confirmed tumor response on 2 consecutive evaluations ≥ 4 weeks apart

Progression-free survival rate at 6 months after randomization
Time to disease progression
Time to treatment failure
Overall survival at 1 year after randomization

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.

van Cruijsen H, Voest EE, van Herpen CM, et al.: Phase I evaluation of AZD2171, a highly potent, selective VEGFR signaling inhibitor, in combination with gefitinib, in patients with advanced tumors. [Abstract] J Clin Oncol 24 (Suppl 18): A-3017, 125s, 2006.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Alex Adjei, MD, PhD, Protocol chair		Ph: 507-538-0268; 800-685-6825 Email: alex.adjei@roswellpark.org
Donald Northfelt, MD, FACP, Protocol co-chair		Ph: 507-284-1159 Email: northfelt.donald@mayo.edu
Grace Dy, MD, Protocol co-chair		Ph: 507-284-2511
Debabrata Mukhopadhyay, PhD, Protocol co-chair		Ph: 507-284-2511

Registry Information
Official Title		A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer
Trial Start Date		2007-06-15
Trial Completion Date		2008-07-01 (estimated)
Registered in ClinicalTrials.gov		NCT00326599
Date Submitted to PDQ		2006-02-10
Information Last Verified		2008-12-08
NCI Grant/Contract Number		CA25224

Back to Top