Clinical trial NCT00030641: Docetaxel With or Without Oblimersen in Treating Patients With Non-Small Cell Lung Cancer
Official title: Randomized Study of Docetaxel Versus Docetaxel Plus Genasense™ (G3139; Bcl-2 Antisense Oligonucleotide) in Patients With Previously Treated Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
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: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy such as docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of docetaxel by making the tumor cells more sensitive to the drug. It is not yet known if docetaxel is more effective with or without oblimersen in treating non-small cell lung cancer.

PURPOSE: Randomized phase II/III trial to compare the effectiveness of docetaxel with or without oblimersen in treating patients who have relapsed or refractory non-small cell lung cancer that has been previously treated.

Detailed description: OBJECTIVES:

* Compare the survival of patients with non-small cell lung cancer treated with docetaxel with or without oblimersen (G3139).
* Compare the proportion of major antitumor responses in patients treated with these regimens.
* Compare the response duration and time to progression in patients treated with these regimens.
* Compare the safety and clinical benefit of these regimens, in terms of changes in performance status and tumor-related symptoms, in these patients.
* Compare the proportion of patients surviving 6 and 12 months after treatment with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to response to prior first-line chemotherapy regimen (progression vs stable disease, partial response, or complete response), ECOG performance status (0-1 vs 2), and prior paclitaxel treatment (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oblimersen (G3139) IV continuously on days 1-7 and docetaxel IV over 1 hour on day 5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease upon completion of 8 courses may receive 8 or more additional courses at physician's discretion.
* Arm II: Patients receive docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Upon completion of 8 courses, patients may continue to receive docetaxel off study at physician's discretion.

Patients are followed every 9 weeks for up to 18 months.

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of non-small lung cancer (NSCLC)

  * Stage IIIB (malignant pleural/pericardial effusion) or IV
  * Relapsed or refractory disease
* Measurable disease that has not been irradiated
* Previously treated with 1, and only 1, cytotoxic chemotherapy regimen in the neoadjuvant, adjuvant, or metastatic setting
* No untreated or symptomatic brain metastases or leptomeningeal disease

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 12 weeks

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3 (without growth factor support)
* Platelet count at least 100,000/mm\^3
* No bleeding or coagulation disorder

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* ALT and AST no greater than 2.5 times ULN
* Alkaline phosphatase no greater than 2.5 times ULN
* Albumin at least 3.0 g/dL
* PT no greater than 1.5 times ULN OR INR no greater than 1.3
* PTT no greater than 1.5 times ULN
* No chronic hepatitis
* No chronic cirrhosis

Renal:

* Creatinine no greater than 1.5 times ULN

Cardiovascular:

* No New York Heart Association class III or IV heart disease
* No uncontrolled congestive heart failure

Pulmonary:

* No severe pulmonary disease
* No requirement for oxygen due to pneumonectomy
* No severe pleural effusion secondary to NSCLC

Immunologic:

* HIV negative
* No active infection
* No active autoimmune disease

Other:

* No other concurrent active cancer
* No uncontrolled diabetes mellitus
* No uncontrolled seizure disorder
* No peripheral neuropathy grade 2 or greater
* No active peptic ulcer disease
* No other significant medical disease
* No intellectual, emotional, or physical disability that would preclude study participation
* No neurologic disorders, overt psychosis, mental disability, or evidence of a limited capacity to give informed consent or to comply with study treatment
* No known hypersensitivity to phosphorothioate-containing oligonucleotides
* No history of hypersensitivity to drugs containing the excipient Tween 80 (polysorbate 80)
* Satisfactory venous access for multi-day continuous infusion
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 3 weeks since prior cytokines or vaccine therapy for NSCLC
* At least 3 weeks since prior immunotherapy or biologic therapy for NSCLC
* No concurrent anticancer biologic therapy

Chemotherapy:

* See Disease Characteristics
* At least 3 weeks since prior chemotherapy for NSCLC
* No prior docetaxel
* No other concurrent anticancer chemotherapy

Endocrine therapy:

* No concurrent corticosteroids\* except for the following conditions:

  * CNS disease
  * Underlying lung disease NOTE: \*Dose must be stable or decreasing for at least 4 weeks before study participation

Radiotherapy:

* See Disease Characteristics
* At least 3 weeks since prior radiotherapy for NSCLC
* No prior radiotherapy to 25% or more of bone marrow (e.g., whole pelvis)
* No concurrent anticancer radiotherapy

Surgery:

* At least 3 weeks since prior surgery for NSCLC
* No prior organ allograft

Other:

* Recovered from prior therapy
* Prior first-line epidermal growth factor receptors (EGFR) administered with cytotoxic therapy are allowed
* At least 3 weeks since prior investigational drugs
* At least 3 weeks since other prior therapy NSCLC
* No prior anticancer therapy subsequent to the first (and only) prior cytotoxic chemotherapy regimen
* No prior second-line EGFR therapy
* No prior oblimersen (G3139)
* No other concurrent investigational or anticancer therapies
* No concurrent anticoagulation therapy except for warfarin (1 mg/day) for central line prophylaxis

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Montgomery
country: United States
facility: Montgomery Cancer Center
state: Alabama
city: Little Rock
country: United States
facility: Little Rock Hematology-Oncology Associates
state: Arkansas
city: Concord
country: United States
facility: East Bay Medical Oncology
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Medical Oncology Care Associates
state: California
city: San Francisco
country: United States
facility: Pacific Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute at Saint John's Health Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Norwalk
country: United States
facility: Whittingham Cancer Center
state: Connecticut
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists - Northside Office
state: Georgia
city: Augusta
country: United States
facility: Augusta Oncology Associates
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Hematology Oncology Services
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Omaha
country: United States
facility: Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
state: Nebraska
city: Summit
country: United States
facility: Summit Medical Group, P.A.
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: North General Hospital
state: New York
city: Oklahoma City
country: United States
facility: Veterans Affairs Medical Center - Oklahoma City
state: Oklahoma
city: Charleston
country: United States
facility: Charleston Cancer Center
state: South Carolina
city: Arlington
country: United States
facility: Arlington Cancer Center
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Harold Simmons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Weatherford
country: United States
facility: Texas Cancer Care
state: Texas
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Yakima
country: United States
facility: Yakima Regional Cancer Care Center
state: Washington
city: Morgantown
country: United States
facility: Morgantown Internal Medicine Group
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Ste-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Kaluga Region
country: Russian Federation
facility: Medical Radiological Research Center RAMS
city: Moscow
country: Russian Federation
facility: Russian Academy of Medical Sciences Cancer Research Center
city: Moscow
country: Russian Federation
facility: P.A. Hertzen Research Oncology Institute
city: Saint Petersburg
country: Russian Federation
facility: Municipal Oncological Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Petrov Research Institute of Oncology
Study officials:
affiliation: Genta Incorporated
name: Deborah Braccia
role: STUDY_CHAIR
References: