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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00085228
First received: June 10, 2004
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Prostate Cancer
Biological: oblimersen sodium
Drug: docetaxel
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Prostate-specific antigen response as measured by Bubley criteria every course until progression or after 12 courses [ Designated as safety issue: No ]
  • Severe toxic events as measured by CTCAE v3.0 every course until progression or after 12 courses [ Designated as safety issue: Yes ]

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 [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: Yes ]
  • Objective response as measured by RECIST every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death [ Designated as safety issue: No ]
  • Overall survival as measured by Logrank every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death [ Designated as safety issue: No ]

Enrollment: 116
Study Start Date: April 2004
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085228

Locations
Austria
Kaiser Franz Josef Hospital
Vienna, Austria, A-1100
Belgium
Onze Lieve Vrouw Ziekenhuis Aalst
Aalst, Belgium, B-9300
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
Institut Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Denmark
Rigshospitalet - Copenhagen University Hospital
Copenhagen, Denmark, 2100
France
CHU de Grenoble - Hopital de la Tronche
Grenoble, France, 38043
Israel
Assaf Harofeh Medical Center
Zerifin, Israel, 70300
Italy
Ospedale S. Camillo-Forlanini
Rome, Italy, 00152
Netherlands
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, Netherlands, 1105 AZ
Poland
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
Portugal
Hospital Desterro
Lisboa, Portugal, 2700
Spain
Hospital General Universitari Vall d'Hebron
Barcelona, Spain, 08035
United Kingdom
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Western Infirmary
Glasgow, Scotland, United Kingdom, G11 6NT
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Cora N. Sternberg, MD, FACP Azienda Ospedaliera S. Camillo-Forlanini
  More Information

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00085228     History of Changes
Other Study ID Numbers: EORTC-30021, EORTC-30021, AVENTIS-AVE3139E/2501
Study First Received: June 10, 2004
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014