Prostate Cancer, Androgen Deprivation Withdrawal and Intermittent Chemotherapy

Advanced Prostate Cancer Clinical Trial

— PON-PC-02  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01224405
• Other study ID #: EudraCT 2010-019004-24
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 3, 2010
• Last updated: October 19, 2010
• Start date: April 2010
• Est. completion date: April 2016

Study information

• Verified date: June 2010
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: April 2016
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
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	Davide Perroni	Saluzzo	Cuneo
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

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Toxicity	Toxicity graded according to NCI Criteria	six years	Yes
Secondary	Progression free survival	Progression free survival measured according to Prostate Cancer Clinical Trials Working Group	six years	Yes
Secondary	Quality of life	Quality of life evaluated according to FACT-P questionnaire	six years	Yes
Secondary	Pain	Pain response evaluated by Mc-Gill Pain Questionnaire	six years	Yes
Secondary	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	Yes