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

Androgen Deprivation Withdrawal Versus Maintenance and Intermittent Chemotherapy Versus Continuous in Prostate Cancer Patients With Castrate Resistant Disease

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

Study Overview

• Status: Unknown
• Conditions: Advanced Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel + LH-RH analogues; Drug: Docetaxel; Drug: Docetaxel; Drug: Continuous Docetaxel; Drug: Continuous Docetaxel

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 Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

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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

4

Arms and Interventions

Participant Group / 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.; 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.
Experimental: intermittent arm; Intermittent Docetaxel	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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	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.	six years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Toxicity graded according to NCI Criteria	six years
Progression free survival	Progression free survival measured according to Prostate Cancer Clinical Trials Working Group	six years
Quality of life	Quality of life evaluated according to FACT-P questionnaire	six years
Pain	Pain response evaluated by Mc-Gill Pain Questionnaire	six years
Cost Analysis	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.	six years

Collaborators and Investigators

• Sponsor: 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

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): August 1, 2010
• Study Completion (Anticipated): April 1, 2016

Study Registration Dates

• First Submitted: September 3, 2010
• First Submitted That Met QC Criteria: October 19, 2010
• First Posted (Estimate): October 20, 2010

Study Record Updates

• Last Update Posted (Estimate): October 20, 2010
• Last Update Submitted That Met QC Criteria: October 19, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: EudraCT 2010-019004-24