Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery

National Cancer Institute (NCI)

Status and phase: Completed; Phase 3

Conditions: Stage IIIB Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Adenocarcinoma of the Lung; Stage IIIA Non-small Cell Lung Cancer; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer

Treatments: Radiation: radiation therapy; Other: placebo; Drug: paclitaxel; Drug: carboplatin; Drug: shark cartilage extract AE-941; Drug: cisplatin; Drug: vinorelbine tartrate

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00005838

U10CA045809 (U.S. NIH Grant/Contract)

CDR0000067853 (Registry Identifier)

NCI-2012-02725

ID99-303

Details and patient eligibility

About

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

Full description

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.

Enrollment: 756 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically or cytologically confirmed newly diagnosed, untreated, unresectable stage IIIA or stage IIIB non-small cell lung cancer

  • Squamous cell carcinoma, adenocarcinoma, or large cell carcinoma of the lung
  • Mixed tumors allowed if non-small cell elements identified
  • Contralateral supraclavicular and/or scalene lymph node involvement allowed
  • No disease extending into the cervical region

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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756 participants in 2 patient groups, including a placebo group

Arm I (shark cartilage extract AE-941)

Experimental group

Description:

Patients receive oral AE-941 (Neovastat) 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.

Treatment:

Drug: vinorelbine tartrate

Drug: cisplatin

Drug: shark cartilage extract AE-941

Drug: paclitaxel

Drug: carboplatin

Radiation: radiation therapy

Arm II (placebo)

Placebo Comparator group

Description:

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.

Treatment:

Drug: vinorelbine tartrate

Drug: cisplatin

Drug: paclitaxel

Drug: carboplatin

Other: placebo

Radiation: radiation therapy