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

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

Study Overview

• Status: Completed
• Conditions: Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Adenocarcinoma of the Lung; Large Cell Lung Cancer; Adenosquamous Cell Lung Cancer
• Intervention / Treatment: Other: placebo; Radiation: radiation therapy; Drug: paclitaxel; Drug: vinorelbine tartrate; Drug: cisplatin; Drug: carboplatin; Drug: shark cartilage extract AE-941

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 756
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (shark cartilage extract AE-941); 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.	Radiation: radiation therapy; Undergo radiotherapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; TAX; Drug: vinorelbine tartrate; Given IV; Other Names: Eunades; navelbine ditartrate; NVB; VNB; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: shark cartilage extract AE-941; Given orally; Other Names: AE-941; Neovastat; Neovastat/AE-941
Placebo Comparator: Arm II (placebo); 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.	Other: placebo; Given orally; Other Names: PLCB; Radiation: radiation therapy; Undergo radiotherapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; TAX; Drug: vinorelbine tartrate; Given IV; Other Names: Eunades; navelbine ditartrate; NVB; VNB; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Survival distributions will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted to illustrate the comparative survival experience of both groups over the entire study period.	From randomization until date of death or last follow-up, assessed up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival every 3 months	Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.	From randomization until disease progression, assessed up to 7 years
Tumor response rate	Will be compared by chi-square test.	Up to 7 years
Tumor response duration	Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.	From first observation of at least a partial response to detection of disease progression or death due to any cause, assessed up to 7 years
Metastasis-free survival	Will be compared by use of the log-rank test. The stratified log-rank test (nominal or categorical covariates) may be used to simultaneously control for important prognostic factors. Kaplan-Meier curves will also be plotted.	From randomization until metastasis documented by imaging procedures, assessed up to 7 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: National Center for Complementary and Integrative Health (NCCIH); Radiation Therapy Oncology Group
• Investigators: Principal Investigator: Charles Lu, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Cisplatin; Vinorelbine
• Other Study ID Numbers: NCI-2012-02725; U10CA045809 (U.S. NIH Grant/Contract); ID99-303; CDR0000067853 (Registry Identifier: PDQ (Physician Data Query))