Multicenter, Open-Ended, Double-Blind, Placebo-Controlled, Phase III Study of AE-941 in Addition to Combined Modality Treatment (Chemotherapy/Radiotherapy) for Locally Advanced Unresectable Non-Small Cell Lung Cancer
Multicenter, Open-Ended, Double-Blind, Placebo-Controlled, Phase III Study of AE-941 in Addition to Combined Modality Treatment (Chemotherapy/Radiotherapy) for Locally Advanced Unresectable Non-Small Cell Lung Cancer
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. AE-941 may help shrink or slow the growth of non-small cell lung cancer cells. It is not yet known if combination chemotherapy plus radiation therapy is more effective with or without AE-941 for non-small cell lung cancer. This randomized phase III trial is studying combination chemotherapy and radiation therapy given with AE-941 to see how well they work compared to combination chemotherapy and radiation therapy alone in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery
PRIMARY OBJECTIVES:
I. Determine the overall survival of patients with unresectable stage IIIA or IIIB non-small cell lung cancer treated with induction platinum-based chemotherapy and radiotherapy with or without AE-941 (Neovastat).
II. Determine the progression-free survival, tumor response, tumor response duration, and metastasis-free survival of patients treated with these regimens.
III. Determine the tolerability of this regimen in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to stage (IIIA vs IIIB), type of platinum-based induction chemotherapy to be received (cisplatin and vinorelbine vs carboplatin and paclitaxel), and gender. Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive oral AE-941 (Neovastat) twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
Arm II: Patients receive oral placebo twice daily beginning on day 1 or within 10 days of initiation of chemotherapy.
All patients receive induction chemotherapy with 1 of the following platinum-based regimens: cisplatin IV on days 1, 22, 50, and 71 and vinorelbine IV on days 1, 8, 22, 29, 50, 57, 71, and 78 carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on days 1, 22, 50, 57, 64, 71, 78, and 85.
All patients receive radiotherapy beginning on day 50 for 6 weeks. Treatment in both arms continues in the absence of unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 756 patients (378 per treatment arm) will be accrued for this study within 36 months.
Inclusion Criteria:
Histologically or cytologically confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer
At least 1 bidimensionally or unidimensionally measurable lesion
No pleural effusion unless cytologically negative or too small to safely aspirate
Not scheduled for curative cancer surgery
Performance status - ECOG 0-1
Absolute neutrophil count greater than 1,500/mm^3
Platelet count greater than 100,000/mm^3
Hematocrit greater than 30%
SGOT or SGPT less than 1.5 times upper limit of normal
Bilirubin normal
Creatinine less than 1.5 mg/dL
Creatinine clearance greater than 60 mL/min
No other major medical or psychiatric illness that would preclude study participation or consent
No medical condition that interferes with oral medication intake and/or absorption (gastrectomy or major intestinal resection)
No grade 2 or greater peripheral neuropathy unless secondary to mechanical etiology
No hypersensitivity to fish products
No more than 10% weight loss within past 3 months
No other malignancy within past 3 years except inactive carcinoma in situ of the cervix or nonmelanoma skin cancer
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
At least 30 days since prior chemotherapy
See Disease Characteristics
Recovered from prior major surgery
At least 30 days since prior shark cartilage products
No other concurrent investigational anticancer agents
No other concurrent cartilage products
No other concurrent investigational agents
No concurrent amifostine or other radioprotectants
No concurrent enrollment in other clinical trials