Chemotherapy and Radiation Therapy With or Without Efaproxiral in Treating Patients With Stage III Non-Small Cell Lung Cancer

A Phase III Randomized, Open-Label Comparative Study of Induction Chemotherapy Followed by Thoracic Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Patients With Locally Advanced Unresectable (Stage IIIA/IIIB) Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as efaproxiral may make the tumor cells more sensitive to radiation therapy. It is not yet known if chemotherapy combined with radiation therapy is more effective with or without efaproxiral in treating non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy combined with radiation therapy with or without efaproxiral in treating patients who have stage III non-small cell lung cancer.

Study Overview

• Status: Withdrawn
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: cisplatin; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Procedure: radiation therapy; Drug: vinorelbine ditartrate; Drug: efaproxiral

Detailed Description

OBJECTIVES:

• Compare the overall survival of patients with stage IIIA or IIIB non-small cell lung cancer treated with induction chemotherapy followed by radiotherapy with or without efaproxiral.
• Compare time to progression, response rate, and pattern of failure of patients treated with these regimens.
• Determine the safety of efaproxiral in these patients.
• Determine the pharmacokinetics of efaproxiral in these patients.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to chemotherapy regimen, Karnofsky performance status (70-80% vs 90-100%), and disease stage (IIIA vs IIIB).

• Induction therapy phase: Patients receive 1 of the following induction chemotherapy regimens:

  • Paclitaxel and carboplatin: Patients receive paclitaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for a total of 2 courses.
  • Cisplatin and gemcitabine: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15. Treatment repeats every 28 days for a total of 2 courses.
  • Cisplatin and vinorelbine: Patients receive cisplatin IV on day 1 and vinorelbine IV on days 1, 8, and either 15 or 22. Treatment repeats every 28 days for a total of 2 courses.

• Randomized phase: Within 42 days after completion of chemotherapy, patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive efaproxiral IV over 30-45 minutes with supplemental oxygen and then undergo concurrent radiotherapy 5 days a week for 7 weeks.
  • Arm II: Patients receive supplemental oxygen and undergo radiotherapy as in arm I.

Quality of life is assessed at baseline, on days 1 and 16 of radiotherapy, monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 659 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Algemeen Ziekenhuis Middelheim
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center - Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • Cancer Care Ontario-London Regional Cancer Centre
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre
  • Quebec
    • Fleurimont, Quebec, Canada, J1H 5N4
      • CHUS-Hopital Fleurimont
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H2L 4M1
      • Hopital Notre- Dame du CHUM
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
• Israel
  • Beer-Sheva, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Tel Hashomer, Israel, 52621
    • Sheba Medical Center
  • Tel-Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Cancer Center at Lexington Clinic
  • Louisiana
    • Shreveport, Louisiana, United States, 71103-3951
      • Willis - Knighton Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Cancer Center
  • Washington
    • Everett, Washington, United States, 98206
      • Providence Everett Medical Center - Pacific Campus
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler 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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced, unresectable non-small cell lung cancer of 1 of the following subtypes:

  • Adenocarcinoma
  • Squamous cell carcinoma
  • Large cell carcinoma
  • Poorly differentiated carcinoma

• Stage IIIA or IIIB

  • T1 or T2, N2
  • T3, N1 or N2
  • T4, any N
  • Any T, N3
• Histological or cytological confirmation of at least 1 positive lymph node required if the largest mediastinal node that is the basis of stage III disease is less than 2.0 cm in diameter
• Clinically or radiologically measurable disease of at least 2.0 cm
• Partially resected stage IIIB disease allowed provided a measurable lesion remains
• No pleural effusion that is bloody, cytologically positive, or re-accumulated after thoracentesis
• No metastatic disease by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin at least 10 g/dL
• WBC at least 3,000/mm^3
• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No clinically active congestive heart failure
• No unstable angina
• No severe arrhythmia by ECG

Pulmonary

• FVC and FEV_1 at least 50% of normal
• Resting oxygen saturation by pulse oximetry (SpO_2) at least 90% on room air
• Exercise SpO_2 at least 90% on room air

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use effective contraception during and for 30 days after study therapy
• Male patients must use effective contraception during and for 90 days after study therapy
• No loss of more than 10% of body weight within the past 3 months
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No significantly altered mental status or dementia that would preclude giving informed consent
• No active infection
• No other serious underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 28 days since prior biologic therapy
• No concurrent colony-stimulating factors (randomized phase only)
• No biologic therapy during and for 1 month after study therapy
• No immune response modifiers during and for 1 month after study therapy

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• No hormonal therapy during and for 1 month after study therapy

Radiotherapy

• No prior thoracic radiotherapy

Surgery

• See Disease Characteristics
• No prior total surgical resection

Other

• More than 28 days since prior investigational drugs or devices
• No prior efaproxiral
• No other cytotoxic therapy during and for 1 month after study therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc
• Investigators: Study Chair: Hak Choy, MD, Simmons Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 2002

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Estimate): May 10, 2013
• Last Update Submitted That Met QC Criteria: May 8, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antisickling Agents; Gemcitabine; Carboplatin; Paclitaxel; Vinorelbine; Efaproxiral
• Other Study ID Numbers: CDR0000271438; ALLOS-RSR13RT-013ELITE