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

NCT ID: NCT00085228

Last Updated: 2012-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30

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.

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

oblimersen sodium

Intervention Type: BIOLOGICAL

docetaxel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cora N. Sternberg, MD, FACP

Role: STUDY_CHAIR

Azienda Ospedaliera S. Camillo-Forlanini

Locations

Kaiser Franz Josef Hospital

Vienna, , Austria

Onze Lieve Vrouw Ziekenhuis Aalst

Aalst, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Rigshospitalet - Copenhagen University Hospital

Copenhagen, , Denmark

CHU de Grenoble - Hopital de la Tronche

Grenoble, , France

Assaf Harofeh Medical Center

Ẕerifin, , Israel

Ospedale S. Camillo-Forlanini

Rome, , Italy

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, , Netherlands

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Hospital Desterro

Lisbon, , Portugal

Hospital General Universitari Vall d'Hebron

Barcelona, , Spain

Saint Bartholomew's Hospital

London, England, United Kingdom

Western Infirmary

Glasgow, Scotland, United Kingdom

Countries

Austria; Belgium; Denmark; France; Israel; Italy; Netherlands; Poland; Portugal; Spain; United Kingdom

References

Sternberg CN, Dumez H, Van Poppel H, Skoneczna I, Sella A, Daugaard G, Gil T, Graham J, Carpentier P, Calabro F, Collette L, Lacombe D; EORTC Genitourinary Tract Cancer Group. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann Oncol. 2009 Jul;20(7):1264-9. doi: 10.1093/annonc/mdn784. Epub 2009 Mar 17.

Reference Type: RESULT

PMID: 19297314 (View on PubMed)

Sternberg CN, Dumez H, Van Poppel H, et al.: Multicenter randomized EORTC trial 30021 of docetaxel + oblimersen and docetaxel in patients (pts) with hormone refractory prostate cancer (HRPC). [Abstract] American Society of Clinical Oncology 2007 Prostate Cancer Symposium, 22-24 February 2007, Orlando, FL. A-144, 2007.

Reference Type: RESULT

Other Identifiers

EORTC-30021

Identifier Type: -

Identifier Source: secondary_id

AVENTIS-AVE3139E/2501

Identifier Type: -

Identifier Source: secondary_id

EORTC-30021

Identifier Type: -

Identifier Source: org_study_id