Prostate Cancer, Androgen Deprivation Withdrawal and Intermittent Chemotherapy (PON-PC-02)

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The study includes the recruitment of patients with advanced prostate cancer resistant to chemical castration This is a multicenter prospective trial randomized phase III

Condition or disease	Intervention/treatment	Phase
Advanced Prostate Cancer	Drug: Docetaxel + LH-RH analogues; Drug: Docetaxel; Drug: Continuous Docetaxel	Phase 3

Detailed Description:

The study includes the recruitment of patients with advanced prostate cancer resistant to chemical castration This is a multicenter prospective trial randomized phase III This study design that includes a double randomizzzazione aims generally demonstrating non-inferiority in terms of survival of the suspension dell'ormonoterapia versus the maintenance and / or administration of intermittent versus continuous administration of chemotherapy in patients with prostate cancer resistant to chemical castration I started to line chemotherapy with Docetaxel.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	600 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Androgen Deprivation Withdrawal Versus Maintenance and Intermittent Chemotherapy Versus Continuous in Prostate Cancer Patients With Castrate Resistant Disease
Study Start Date :	April 2010
Actual Primary Completion Date :	August 2010
Estimated Study Completion Date :	April 2016

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Treatment arm; ten docetaxel cycles + maintenance androgen deprivation.	Drug: Docetaxel + LH-RH analogues; Docetaxel will be administered at a dose of 75 mg/m2 per square meter as a 1-hour intravenous infusion on day 1 every 21 days in association to 5 mg of prednisone orally twice daily. In patients randomised to arms A up to 10 cycles of docetaxel will be planned in association to maintenance of LH-RH analogues administration.
Experimental: suspension arm; Ten Docetaxel cycles + stop androgen deprivation therapy	Drug: Docetaxel; Docetaxel will be administered at a dose of 75 mg/m2 per square meter as a 1-hour intravenous infusion on day 1 every 21 days in association to 5 mg of prednisone orally twice daily. In patients randomised to arms B up to 10 cycles of docetaxel will be planned, in association to stopping LH-RH analogues.
Experimental: intermittent arm; Intermittent Docetaxel	Drug: Docetaxel; Patients randomised in the arms AB1 (intermittent docetaxel) will suspend treatment after at least 4 cycles if their PSA level will be reduced >50%. Docetaxel treatment will be resumed when the serum PSA will rise by >50% from the lowest PSA level recorded and will be >10 ng/mL or when there will be other evidence of disease progression. PSA progression must to be confirmed with a second assessment after 2 weeks before deciding to resume docetaxel administration.
Active Comparator: Continuous arm; Continuous Docetaxel	Drug: Continuous Docetaxel; Patients randomised in the arms AB2 (continuous docetaxel) will continue treatment up to ten cycles after even if their PSA level at 4 cycles will be reduced >50% or will reach a level <4 ng/mL. Drug: Continuous Docetaxel; Patients randomised in the arms AB1(intermittent docetaxel) will continue treatment up to ten cycles even if their PSA level after 4 cycles will be reduced >50% or will reach a level <4 ng/mL.

Outcome Measures

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Primary Outcome Measures :

1. overall survival [ Time Frame: six years ]
   The primary aim of the study will be the demonstration of non inferiority in terms of overall survival of stopping androgen deprivation therapy (arm B) versus maintenance androgen deprivation therapy (arms A) and intermittent docetaxel therapy (arm AB1) versus continuous docetaxel therapy (arms AB2) up to ten cycles.

Secondary Outcome Measures :

1. Toxicity [ Time Frame: six years ]
   Toxicity graded according to NCI Criteria
2. Progression free survival [ Time Frame: six years ]
   Progression free survival measured according to Prostate Cancer Clinical Trials Working Group
3. Quality of life [ Time Frame: six years ]
   Quality of life evaluated according to FACT-P questionnaire
4. Pain [ Time Frame: six years ]
   Pain response evaluated by Mc-Gill Pain Questionnaire
5. Cost Analysis [ Time Frame: six years ]
   A cost minimization analysis will be performed in order to find if there is a treatment strategy that may achieve the same outcome for least cost. The analysis will focus on the direct medical costs of each treatment, collected at patient level.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. age over 18 years,
2. histologically documented adenocarcinoma of the prostate,
3. written informed consent to the study,
4. Castrate resistant metastatic prostate cancer in the presence of castrate levels of testosterone (<50 ng/ml) and eligible to docetaxel chemotherapy. The condition of castrate resistant prostate cancer is the defined either as the documentation of a new metastasis or PSA increase more than 50% or increase more than 25% from a lower PSA value during previous hormone therapy in case of disease response or stabilization to previous hormone therapy, respectively. Absolute PSA increase should be greater than 5 ng/ml,
5. an elevated PSA level must have been documented within 4 weeks of initiating docetaxel chemotherapy,
6. more than 4 weeks since major surgery and fully recovered,
7. more than 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to grade 1 or less,
8. more than 8 weeks since the last dose of strontium or samarium,
9. ECOG Performance Status more than/equal to 2,
10. life expectancy >6 months,
11. required initial laboratory values: absolute neutrophil count > 1500/ul Platelets > 100,000/ul., Hemoglobin > 8.0 g/dl, Creatinine, SGOT, SGPT less than 2.0 X upper limit of normal, Bilirubin less than/equal to upper limit of normal (ULN).
12. Appropriate patient compliance

Exclusion Criteria:

1. Patients with increased serum PSA levels with negative bone scan and CT scan.
2. Prior systemic chemotherapy for prostate cancer. Prior neoadjuvant or adjuvant chemotherapy is permitted if there was no evidence of disease relapse within 12 months of the last dose of chemotherapy,
3. Peripheral neuropathy >grade 1,
4. myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (NYHA Class III or higher) or uncontrolled cardiac arrhythmia,
5. patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80,
6. poorly controlled diabetes (fasting blood glucose >250) despite optimization of medical therapy, peptic ulcers or other contraindications to steroid therapy,
7. previous history of malignant disease with the exception of non melanoma skin cancer curatively treated,
8. significant neurologic or psychiatric diseases preventing patients to give a valid informed consent,
9. brain metastases,
10. prisoner status

11. because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded.

Contacts and Locations

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Locations

Italy
Davide Perroni
Saluzzo, Cuneo, Italy
Roberto Faggiuolo
Alba, Italy
Franco Testore
Asti, Italy
Mario Clerico
Biella, Italy
Andrea Martoni
Bologna, Italy
Massimo Aglietta
Candiolo (Torino), Italy
Alberto Muzio
Casale Monferrato, Italy
Mario Botta
Casale Monferrato, Italy
Rodolfo Passalacqua
Cremona, Italy
Marco Merlano
Cuneo, Italy
Luigi Toniolo
Garbagnate Milanese, Italy
Sergio Bretti
Ivrea, Italy
Giovanni Ucci
Lodi, Italy
Pierfranco Conte
Modena, Italy
Carla Sculli
Mondovì, Italy
Oscar Alabiso
Novara, Italy
Bruno Castagneto
Novi Ligure, Italy
Giovanna Succu
Nuoro, Italy
Alfredo Berruti
Orbassano (Torino), Italy
Luigi Dogliotti
Orbassano (Torino), Italy
Luigi Cavanna
Piacenza, Italy
Giorgio Cruciani
Ravenna, Italy
Corrado Boni
Reggio Emilia, Italy
Riccardo Ratti
Sanremo, Italy
Francesco Ferrau
Taormina, Italy
Fausto Roila
Terni, Italy
Carlo Alberto Raucci
Torino, Italy
Guido Vietti Ramus
Torino, Italy
Libero Ciuffreda
Torino, Italy
Gianpiero Fasola
Udine, Italy
Sergio Cozzi
Verbania, Italy
Domenico Amoroso
Viareggio, Italy

Sponsors and Collaborators

University of Turin, Italy

Investigators

Study Chair:	Alfredo Berruti, PHD	Medical Oncology - Hospital San Luigi Gonzaga Orbassano (TO) - Italy
Study Director:	Bruno Castagneto, MD	Medical Oncology - Hospital San Giacomo of Novi Ligure (AL) Italy
Principal Investigator:	Marcello Tucci, MD	Medical Oncology - Hospital San Luigi Gonzaga of Orbassano (TO) - Italy

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Alfredo Berruti, Dipartimento Scienze Cliniche e Biologiche Università di Torino
ClinicalTrials.gov Identifier:	NCT01224405 History of Changes
Other Study ID Numbers:	EudraCT 2010-019004-24
First Posted:	October 20, 2010
Last Update Posted:	October 20, 2010
Last Verified:	June 2010

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Docetaxel; Androgens	Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs