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

Stage IIIB Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005838
• Other study ID #: NCI-2012-02725
• Secondary ID: ID99-303U10CA045
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2000
• Last updated: January 22, 2013
• Start date: March 2000

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 756
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Lung
• Adenosquamous Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Large Cell Lung Cancer
• Lung Neoplasms
• Squamous Cell Lung Cancer
• Stage IIIA Non-small Cell Lung Cancer
• Stage IIIB Non-small Cell Lung Cancer

Intervention

Drug:
• shark cartilage extract AE-941
Given orally

Other:
• placebo
Given orally

Drug:
• cisplatin
Given IV
• vinorelbine tartrate
Given IV
• carboplatin
Given IV
• paclitaxel
Given IV

Radiation:
• radiation therapy
Undergo radiotherapy

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	National Center for Complementary and Integrative Health (NCCIH), Radiation Therapy Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Tumor response rate	Will be compared by chi-square test.	Up to 7 years	No
Secondary	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	No
Secondary	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	No