Polyglutamate Paclitaxel Compared With Gemcitabine or Vinorelbine in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

CT-2103 vs Gemcitabine or Vinorelbine for the Treatment of PS = 2 Patients With Chemotherapy Naive Advanced Non-Small Cell Lung Cancer (NSCLC): A Phase III Study

RATIONALE: 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. It is not yet known whether polyglutamate paclitaxel is more effective than gemcitabine or vinorelbine in treating non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of polyglutamate paclitaxel with that of gemcitabine or vinorelbine in treating patients who have stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: vinorelbine tartrate; Drug: paclitaxel poliglumex

Detailed Description

OBJECTIVES:

• Compare the efficacy of polyglutamate paclitaxel (CT-2103) vs gemcitabine or vinorelbine, in terms of duration of overall survival, in patients with stage IIIB or IV or recurrent non-small cell lung cancer who have a performance status of 2.
• Compare the safety of these regimens in these patients.
• Compare the disease control (percentage of patients with no disease progression for at least 12 weeks) and time to progression in patients treated with these regimens.
• Compare the response rate in patients with measurable disease treated with these regimens.
• Compare the improvement in lung cancer symptoms in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender, disease stage (IV vs other), geographic location (US vs Western Europe and Canada vs the rest of the world), and prior brain metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive polyglutamate paclitaxel (CT-2103) IV over 10 minutes on day 1 every 21 days.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 every 28 days OR vinorelbine IV over 6-10 minutes on days 1, 8, and 15 every 21 days.

Treatment repeats in both arms for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 weeks and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 13 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Cooper Green Hospital
  • California
    • Gilroy, California, United States, 95020
      • Medical Oncology/Hematology
  • Florida
    • Coral Springs, Florida, United States, 33065
      • Northwest Oncology and Hematology Associates
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Midwest Cancer Research Group, Incorporated
  • Nevada
    • Reno, Nevada, United States, 89502
      • Medschool Associates North
  • New York
    • Latham, New York, United States, 12110-0610
      • New York Oncology Hematology, P.C. - Latham
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Clinical Research Services
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Charleston Hematology-Oncology, P.A.
  • Washington
    • Everett, Washington, United States, 98201
      • Western Washington Medical Group
    • Olympia, Washington, United States, 98502
      • Western Washington Oncology, Incorporated

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following criteria:

  • Locally advanced or recurrent disease previously treated with radiotherapy and/or surgery
  • Stage IIIB and not a candidate for combined modality therapy
  • Stage IV
• No evidence of small cell carcinoma, carcinoid, or mixed small cell/non-small cell histology

• Cytological diagnosis must be based on the following:

  • No cellular diagnosis by sputum cytology alone
  • Cytologic specimens obtained from brushings, washings, or needle aspiration of a defined lesion or pleural effusion are acceptable
• Measurable or nonmeasurable disease

• Brain metastases allowed provided patient received prior standard antitumor therapy for CNS metastases (e.g., whole brain radiotherapy, stereotactic radioablation, or surgery) and the following conditions are met:

  • Neurologic function stable for at least 2 weeks before study entry
  • Off steroid therapy or on a tapering regimen
  • Recovered from prior therapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT/SGPT no greater than 2.5 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 2.5 times ULN (except for laboratory documentation that demonstrates bone origin)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No unstable angina
• No myocardial infarction within the past 6 months
• Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided cardiac status has been stable for at least 6 months prior to study entry

Neurologic

• See Disease Characteristics
• No neuropathy greater than grade 1
• No evidence of unstable neurologic symptoms within the past 4 weeks (2 weeks for neurologic symptoms due to brain metastases)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No intolerance to excipients of polyglutamate paclitaxel (e.g., poly-L-glutamic acid, poloxamer 188, dibasic sodium phosphate, or monobasic sodium hydroxide)
• No clinically significant active infection
• No other concurrent primary malignancy except carcinoma in situ or nonmelanoma skin cancer
• No other unstable medical conditions
• No circumstance that would preclude study completion or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic biologic agent for lung cancer

Chemotherapy

• See Disease Characteristics
• No prior systemic chemotherapy for lung cancer including radiosensitizing agents

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior major surgery

Other

• More than 12 weeks since prior participation in any research study or treatment with investigational drugs
• Recovered from prior investigational therapy or stable for 4 weeks before study treatment
• No other concurrent investigational drugs
• No other concurrent systemic antitumor therapy
• No concurrent amifostine
• Concurrent bisphosphonates allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Masking: NONE

Collaborators and Investigators

• Sponsor: CTI BioPharma
• Investigators: Study Chair: Meghann Smith, PPD, Incorporated

Publications and helpful links

General Publications

• O'Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, Hotko YS, Ganul VL, Kostinsky IY, Eisenfeld AJ, Sandalic L, Oldham FB, Bandstra B, Sandler AB, Singer JW. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naive advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):728-34. doi: 10.1097/JTO.0b013e31817c6b68.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2003
• Primary Completion (ACTUAL): October 1, 2004
• Study Completion (ACTUAL): October 1, 2004

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (ESTIMATE): February 6, 2003

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2020
• Last Update Submitted That Met QC Criteria: October 2, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• 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; Gemcitabine; Paclitaxel; Vinorelbine; Paclitaxel poliglumex
• Other Study ID Numbers: CTI-PGT304; CDR0000269908 (REGISTRY: PDQ (Physician Data Query))