Hormone Therapy With or Without Docetaxel And Estramustine in Treating Patients With Prostate Cancer That is Locally Advanced or At High Risk of Relapse

Phase III Randomized Study Of Adjuvant Hormonal Therapy With And Without Docetaxel And Estramustine In Patients With Advanced Prostate Cancer Or With A High Risk Of Relapse

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as nilutamide, bicalutamide, flutamide, or cyproterone may stop the adrenal glands from producing androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy is more effective with or without chemotherapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with or without docetaxel and estramustine in treating patients who have prostate cancer that is locally advanced or at high risk of relapse.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Radiation: radiation therapy; Procedure: conventional surgery; Drug: acetylsalicylic acid; Drug: bicalutamide; Drug: Goserelin Acetate; Drug: Estramustine phosphate sodium

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France, 49100
    • Centre Paul Papin
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France, 33075
    • Hôpital Saint André
  • Boulogne-Billancourt, France, F-92104
    • Hôpital Ambroise Paré
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Cholet, France, 49300
    • Polyclinique du Parc
  • Creteil, France, 94000
    • Centre Hospitalier Universitaire Henri Mondor
  • Hyeres, France, 83400
    • Clinique Sainte-Marguerite
  • La Roche Sur Yon, France, 85025
    • Centre Hospitalier Departemental
  • Lille, France, 59037
    • Centre Hospital Universitaire Hop Huriez
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges
  • Lormont, France, 33310
    • Polyclinique des Quatre Pavillons
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13385
    • CHU de la Timone
  • Marseille, France, 13273
    • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
  • Metz, France, 57038
    • Hopital Notre-Dame de Bon Secours
  • Metz, France, 57072
    • Hopital Clinique Claude Bernard
  • Mont-de-Marsan, France, 40000
    • Centre Hospitalier General de Mont de Marsan
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Montpellier, France, 34295
    • Hopital Lapeyronie-CHU Montpellier
  • Nantes, France, 02
    • Centre Catherine de Sienne
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75248
    • Institut Curie Hopital
  • Paris, France, 75020
    • Hopital de la Croix St. Simon
  • Paris, France, 75674
    • Hôpital Saint Joseph
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Rodez, France, 12027
    • Centre Hospitalier de Rodez
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Cloud, France, 92211
    • Centre Rene Huguenin
  • Saint-Herblain, France, 44805
    • CRLCC Nantes - Atlantique
  • Suresnes, France, 92151
    • Hopital Foch
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Tours, France, 37044
    • Centre Hospitalier Universitaire Bretonneau de Tours
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 79 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Locally advanced disease or at high risk for relapse
• No clinically or radiologically suspected metastases
• Prior lymphadenectomy required

• Meets at least 1 of the following criteria for poor prognosis:

  • Gleason score greater than 7
  • T3 or T4 disease
  • Prostate-specific antigen greater than 20 ng/mL
  • N1 disease

PATIENT CHARACTERISTICS:

Age

• Under 80

Performance status

• ECOG 0-2

Life expectancy

• More than 10 years

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST and ALT no greater than 1.5 times upper limit of normal (ULN)
• Bilirubin no greater than ULN

Renal

• Creatinine less than 1.6 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• No uncontrolled or severe cardiovascular disease
• No prior thrombosis

Pulmonary

• No prior pulmonary embolus

Other

• No active infection
• No intolerance to aspirin
• No other prior malignancy except basal cell skin cancer
• No physical or psychological condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No prior hormonal therapy
• No other concurrent hormonal therapy

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

Other

• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy	Drug: docetaxel; Radiation: radiation therapy; Procedure: conventional surgery; Drug: acetylsalicylic acid; Other Names: Aspirin; Drug: bicalutamide; Other Names: CASODEX®; Drug: Goserelin Acetate; Other Names: ZOLADEX®; Drug: Estramustine phosphate sodium
Active Comparator: Without Chemotherapy	Radiation: radiation therapy; Procedure: conventional surgery; Drug: bicalutamide; Other Names: CASODEX®; Drug: Goserelin Acetate; Other Names: ZOLADEX®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.	From randomization to disease progression or death, up to 15 years.
Biological response: Prostate-specific antigen (PSA) level	The biological response is defined as a non-detectable serum PSA level (<0.1 ng/ml)	3 months
Cancer progression as measured by ultrasound	Defined as a decrease of at least 20% in prostate volume detected by ultrasound after the neo-adjuvant treatment	From randomization to disease progression, up to 15 years.
Clinical progression-free survival	The clinical progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse (based on bone scintigraphy, pelvic scan, or MRI evaluation).	From randomization to disease progression or death, up to 15 years.
Overall survival	The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether SRBT improves overall survival compared to standard of care.	From randomization to death from any cause, up to 15 years.
Acute and late toxicity during the study	The National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.	Throughout study completion, up to 15 years.
Quality of life questionnaire - Core 30 (QLQ-C30)	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At baseline, 3 months, and 1 year

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Sanofi; AstraZeneca

Publications and helpful links

General Publications

• Fizazi K, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Flechon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Lagrange JL, Chinet-Charrot P, Linassier C, Deplanque G, Beuzeboc P, Geneve J, Davin JL, Tournay E, Culine S. A phase III trial of docetaxel-estramustine in high-risk localised prostate cancer: a planned analysis of response, toxicity and quality of life in the GETUG 12 trial. Eur J Cancer. 2012 Jan;48(2):209-17. doi: 10.1016/j.ejca.2011.10.015. Epub 2011 Nov 24.
• Fizazi K, Lesaunier F, Delva R, et al.: A phase III trial of docetaxel-estramustine in high-risk localized prostate cancer (GETUG 12 trial): design, tolerance, response, and quality of life (QOL). [Abstract] 2010 Genitourinary Cancers Symposium, March 5-7, 2010, San Francisco, California. A-7, 2010.
• Fizazi K, Gravis G, Culine S: The GETUG 12 trial, a phase III randomized trial of docetaxel-estramustine in high-risk localized prostate cancer: clinical design and current status. [Abstract] 2006 Prostate Cancer Symposium, February 24-26, 2006, San Francisco, CA. A-153, 2006.
• Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Flechon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. doi: 10.1016/S1470-2045(15)00011-X. Epub 2015 May 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2002
• Primary Completion (Actual): December 21, 2010
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Hormone Antagonists; Androgen Antagonists; Aspirin; Docetaxel; Goserelin; Bicalutamide; Estramustine
• Other Study ID Numbers: GETUG-12 - UC-0160/0203; CDR0000270970; EU-20238