Docetaxel With or Without Oblimersen in Treating Patients With Hormone-Refractory Adenocarcinoma (Cancer) of the Prostate

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00085228

Collaborator

(none)

116

Enrollment

Locations

7.3

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of docetaxel by making tumor cells more sensitive to the drug.

PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with oblimersen works compared to docetaxel alone in treating patients with hormone-refractory adenocarcinoma (cancer) of the prostate.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: oblimersen sodium Drug: docetaxel	Phase 2

Detailed Description

OBJECTIVES:

Primary

Compare the activity of docetaxel with or without oblimersen, in terms of prostate-specific antigen response, in patients with hormone-refractory adenocarcinoma of the prostate.
Compare the toxicity of these regimens in these patients.

Secondary

Compare the time to progression in patients treated with these regimens.
Compare survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, metastatic disease (M0 vs M1 with non-measurable lesions only vs M1 with measurable lesions), prior estramustine (yes vs no), and prior bisphosphonates (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive docetaxel IV over 1 hour on day 5 and oblimersen IV continuously on days 1-7.
Arm II: Patients receive docetaxel IV over 1 hour on day 1. In both arms, treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until progressive disease and then every 16 weeks thereafter.

PROJECTED ACCRUAL: A total of 102 patients (51 per treatment arm) will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Trial of Docetaxel (Taxotere) and Oblimersen (Antisense Oligonucleotide Directed to BCL-2) Versus Taxotere Alone in Patients With Hormone-Refractory Prostate Cancer

Study Start Date :

Apr 1, 2004

Actual Primary Completion Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Prostate-specific antigen response as measured by Bubley criteria every course until progression or after 12 courses []
Severe toxic events as measured by CTCAE v3.0 every course until progression or after 12 courses []

Secondary Outcome Measures

Time to progression as measured by RECIST and Bubley criteria every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death []
Toxicity as measured by CTCAE v3.0 every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death []
Objective response as measured by RECIST every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death []
Overall survival as measured by Logrank every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the prostate
Hormone-refractory disease
Disease progression after prior hormonal therapy with luteinizing hormone-releasing hormone (LH-RH) analogues or orchiectomy and antiandrogens (given together or consecutively)
Prostate-specific antigen (PSA) progression documented by at least 2 increases in PSA values over previous PSA reference value
Must demonstrate continued PSA elevation for at least 6 weeks after discontinuation of antiandrogen therapy
PSA ≥ 5 ng/mL (Hybritech or equivalent) within the past week
Testosterone ≤ 0.5 ng/mL* NOTE: *Patients with medical castration with LH-RH analogue must continue with LH-RH analogue throughout the study
No evidence of painful and/or destructive bone metastases requiring concurrent radiotherapy, bisphosphonates, or bone-seeking radionuclides
Other bone metastases allowed
No clinical evidence of brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

WHO 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
WBC ≥ 3,500/mm^3
Hemoglobin ≥ 10 g/dL

Hepatic

AST and ALT ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ ULN
PTT and PT ≤ 1.5 times ULN OR
INR ≤ 1.3

Renal

Creatinine ≤ 1.5 times ULN OR
Creatinine clearance ≥ 50 mL/min

Cardiovascular

No unstable angina
No uncontrolled hypertension
No deep venous thrombosis within the past 6 months
No cerebrovascular accident, transient ischemic attack, or myocardial infarction within the past 6 months

Pulmonary

No pulmonary embolism
No history of interstitial pneumonitis
No history of pulmonary fibrosis

Other

Adequate venous access
HIV negative
No active infection
No pre-existing neuropathy
No hypersensitivity to phosphorothioates
No hypersensitivity to oligonucleotides or any other component of the oblimersen formulation or to drugs formulated with polysorbate
No psychological, familial, sociological, or geographical condition that would preclude study compliance
No other malignancy within the past 5 years except adequately treated superficial urothelial or skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Prior estramustine allowed
No other prior chemotherapy
No concurrent estramustine

Endocrine therapy

See Disease Characteristics
At least 6 weeks since prior flutamide, bicalutamide, or nilutamide
More than 6 weeks since prior hormonal manipulation with PC-SPES
Concurrent LH-RH agonist allowed
No concurrent antiandrogens

Radiotherapy

See Disease Characteristics
No prior radiotherapy involving > 25% of marrow-producing area
No prior bone-seeking radionuclides
No concurrent radiotherapy (including palliative therapy for painful bone metastases)
No concurrent bone-seeking radionuclides

Surgery

See Disease Characteristics

Other

Prior bisphosphonates allowed
No concurrent anticoagulation except for low-dose warfarin (1 mg/day)
No concurrent regular (daily) intake of opioid analgesics
No other concurrent experimental drugs or anticancer drugs
No concurrent bisphosphonates

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Franz Josef Hospital	Vienna		Austria	A-1100
2	Onze Lieve Vrouw Ziekenhuis Aalst	Aalst		Belgium	B-9300
3	Institut Jules Bordet	Brussels		Belgium	1000
4	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
5	Universitair Ziekenhuis Gent	Ghent		Belgium	B-9000
6	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
7	Rigshospitalet - Copenhagen University Hospital	Copenhagen		Denmark	2100
8	CHU de Grenoble - Hopital de la Tronche	Grenoble		France	38043
9	Assaf Harofeh Medical Center	Zerifin		Israel	70300
10	Ospedale S. Camillo-Forlanini	Rome		Italy	00152
11	Academisch Medisch Centrum at University of Amsterdam	Amsterdam		Netherlands	1105 AZ
12	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw		Poland	02-781
13	Hospital Desterro	Lisboa		Portugal	2700
14	Hospital General Universitari Vall d'Hebron	Barcelona		Spain	08035
15	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
16	Western Infirmary	Glasgow	Scotland	United Kingdom	G11 6NT