Clinical trial NCT00054197: Polyglutamate Paclitaxel Compared With Gemcitabine or Vinorelbine in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: CTI BioPharma
Sponsor class: INDUSTRY
First posted: 2003-02-06
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cooper Green Hospital
state: Alabama
city: Gilroy
country: United States
facility: Medical Oncology/Hematology
state: California
city: Coral Springs
country: United States
facility: Northwest Oncology and Hematology Associates
state: Florida
city: Skokie
country: United States
facility: Midwest Cancer Research Group, Incorporated
state: Illinois
city: Reno
country: United States
facility: Medschool Associates North
state: Nevada
city: Latham
country: United States
facility: New York Oncology Hematology, P.C. - Latham
state: New York
city: Bismarck
country: United States
facility: Clinical Research Services
state: North Dakota
city: Charleston
country: United States
facility: Charleston Hematology-Oncology, P.A.
state: South Carolina
city: Everett
country: United States
facility: Western Washington Medical Group
state: Washington
city: Olympia
country: United States
facility: Western Washington Oncology, Incorporated
state: Washington
Study officials:
affiliation: PPD, Incorporated
name: Meghann Smith
role: STUDY_CHAIR
References:
citation: 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.