Feasibility of a Chemotherapy With Docetaxel-Prednisone for Castration-resistant Metastatic Prostate Cancer Elderly Patients

NCT ID: NCT01254513

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-09
• Study Completion Date: 2017-04-27

Brief Summary

The objective of this study is to evaluate the feasibility of two different chemotherapy protocols with adjusted doses for patients aged 75 and over who often have medical problems other than prostate cancer. Patient will receive Docetaxel either every 3 weeks or weekly. In both cases, chemotherapy is combined with prednisone. The protocol will be considered feasible when patient will receive 6 cycles of chemotherapy (1 cycle = 3 weeks).

Additionally to this primary objective, efficacy will also be evaluated for both protocols as well as tolerance to treatment, quality of life and evolution of geriatric data.

Detailed Description

Standard management of castration-resistant metastatic prostate cancer is represented by chemotherapy with Docetaxel 75 mg/m² every 3 weeks combined with Prednisone since a symptomatic and overall survival benefit was demonstrated.

Although this benefit is independent of age in the study by Tannock (cut-off:69), it does not seem possible to extrapolate these results, obtained in a selected population, to the majority of patients we encounter in daily practice, >= 75 years old and / or unfit.

Retrospective studies have shown that chemotherapy was feasible, at standard or adapted doses in an unselected elderly population with good results in terms of tolerance and efficacy over symptoms.

Our study aims to evaluate prospectively the feasibility of a chemotherapy with Docetaxel/Prednisone administered every 3 weeks (60 mg / m² at D1C1 then 70 mg / m² at D1 for subsequent cycles if tolerance is good) or weekly (35mg / m² at D1 and D8 with Day 1 = Day 21) to patients >= 75 years old, evaluated by comprehensive geriatric assessment, belonging to group 2 "vulnerable" or to group 3 "frail" of the classification proposed by the International Society of Geriatric Oncology (SIOG).

Feasibility is defined as the possibility for a patient to receive 6 cycles of chemotherapy without withdrawal. Reasons for study withdrawal were defined by the GERICO Group and are the followings:

• stop or delay of chemotherapy > 2 weeks
• Necessity to reduce the dose of chemotherapy > 25 %
• febrile neutropenia or non-haematological grade 3 toxicity (except alopecia) according to NCI-CTCAE V4.0.
• Geriatric criterion (Activity of Daily Living (ADL) decrease >= 2 points)

The statistical methodology used is a double randomized phase II after stratification according to the SIOG criteria, based on a Simon Optimum plan.

A pharmacokinetic / pharmacodynamic study is associated to our project, based on a method of population pharmacokinetic. The aim is to highlight predictors of the haematological tolerance of this chemotherapy by evaluating clinical, geriatric and biological parameters.

The results of this study will support the terms of prescription of chemotherapy, in patients aged 75 and over, classified as "vulnerable" or "frail" regarding SIOG criteria, with defined geriatric assessment.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - Docetaxel every 3 weeks + Prednisone

• Docetaxel: 60 mg/m²/day at C1 then 70 mg/m²/day for subsequent cycles every 3 weeks
• Prednisone 10 mg/day continuously

Group Type: EXPERIMENTAL

Docetaxel every 3 weeks + Prednisone

Intervention Type: DRUG

• Docetaxel IV 60 mg/m²/d then IV 70 mg/m²/d for subsequent cycles every 3 weeks
• Prednisone 10 mg/day continuously

Docetaxel weekly+ Prednisone

Intervention Type: DRUG

• Docetaxel weekly 35 mg/m²/day at day 1 and day 8 of each cycle (J1 = J21)
• Prednisone 10 mg/day continuously

Arm B - Docetaxel weekly + Prednisone

• Docetaxel weekly 35 mg/m²/day on day 1 and day 8 of each cycle (J1 = J21)
• Prednisone 10 mg/day continuously

Group Type: EXPERIMENTAL

Docetaxel weekly+ Prednisone

Intervention Type: DRUG

• Docetaxel weekly 35 mg/m²/day at day 1 and day 8 of each cycle (J1 = J21)
• Prednisone 10 mg/day continuously

Interventions

Docetaxel every 3 weeks + Prednisone

• Docetaxel IV 60 mg/m²/d then IV 70 mg/m²/d for subsequent cycles every 3 weeks
• Prednisone 10 mg/day continuously

Intervention Type: DRUG

Docetaxel weekly+ Prednisone

• Docetaxel weekly 35 mg/m²/day at day 1 and day 8 of each cycle (J1 = J21)
• Prednisone 10 mg/day continuously

Intervention Type: DRUG

Other Intervention Names

TAXOTERE; TAXOTERE

Eligibility Criteria

Inclusion Criteria

• Age >= 75
• Histologically proven prostate adenocarcinoma
• Metastatic disease, not pre-treated with chemotherapy refractory to castration
• Hormone refractory prostate cancer is defined as follows:

• Patients with documented testosterone castration (<0.50 ng / ml)
• Patient who received prior hormonal therapy (either orchidectomy or Luteinizing hormone-releasing hormone (LHRH) agonist alone or combined with an anti-androgen)
• Patients should continue primary androgen suppression by LHRH agonist (in case of non-surgical castration)
• For patients treated with anti-androgens prior to inclusion, a wash-out period is required (4 weeks for flutamide and nilutamide, 6 weeks for other products) as well as measured progression after anti-androgen discontinuation.
• Progressive disease under hormonotherapy, with progression defined by

Increase of PSA level (two consecutive increases of PSA compared to baseline with a minimum of one week between both measurements)

OR emergence of a new lesion

OR measurable progressive disease (increase of a previous measurable lesion >= 25% in cross section)

OR progressive bone metastases (defined only by the appearance of a new lesion on bone scan)

OR progressive symptoms (defined as cancer pain Grade 2 according to the NCI-CTC V4.0, despite level 2 analgesics intake).

• Patients of Groups 2 and 3 [ "vulnerable" and "frail"] of SIOG classification
• WHO Performance Status (PS) >= 3
• PSA >= 5 ng / ml
• Neutrophils >= 2.109 /L
• Platelets >= 100.109/L
• Haemoglobin ≥ 9 g/dl
• Bilirubin and SGOT / SGPT <1.5 x ULN (<= 2.5 x ULN if hepatic metastasis)
• creatinine <= 2.5 x ULN
• In case of previous palliative or analgesic radiotherapy, a minimum of 14 days must have elapsed between end of radiotherapy and inclusion into the study
• Previous treatment with bisphosphonates should be continued without change during the study treatment and can not be initiated either within 28 days prior to study entry or during the study
• Signed informed consent by patients, according to local regulations

Exclusion Criteria

• "healthy" or "terminal illness" Groups according to the recommendations of International Society of Geriatric Oncology (SIOG)
• Concomitant or previous malignancy within 5 years prior the study (except basal or squamous in situ cell skin carcinoma)
• Presence of brain metastasis symptoms
• Prior treatment by intravenous radiopharmaceutical agent (e.g. Strontium 89, Samarium lexidronam) within 2 months before study entry
• Initiation of a bisphosphonate therapy within 28 days prior to randomisation
• Any concomitant anticancer treatment (radiotherapy, radiopharmaceutical agent, chemotherapy)
• Patients with uncontrolled infection
• Patients with peripheral neuropathy of grade> 1
• Patients medically unstable (e.g. unstable diabetes, uncontrolled hypertension or decompensated heart failure or myocardial infarct within 3 months)
• Gastro duodenal active ulcer
• Hypersensitivity to study drugs
• Treatment with any experimental drug within 30 days prior to or during the study
• Psychological, familial, sociological or geographical location conditions which do not allow medical monitoring and compliance with study protocol.
• Patients protected by the law or patients placed under protective supervision of adults

• Minimum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Loic Mourey

Role: PRINCIPAL_INVESTIGATOR

Institut Claudius Regaud

Locations

Clinique Claude Bernard

Albi, , France

CHI Annemasse-Bonneville

Ambilly, , France

Centre Paul Papin

Angers, , France

CH de Blois

Blois, , France

Institut Bergonie

Bordeaux, , France

Centre Francois Baclesse

Caen, , France

CH Intercommunal

Castres, , France

Centre Hospitalier de Chambery

Chambéry, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Clinique Sainte Marguerite

Hyères, , France

Chd Vendee

La Roche-sur-Yon, , France

Clinique Hartmann

Levallois-Perret, , France

Centre Oscar Lambret

Lille, , France

Hôpital Saint Vincent de Paul

Lille, , France

Centre Leon Berard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

CHU Nimes

Nîmes, , France

Chr Orleans

Orléans, , France

Institut Curie/Claudius Regaud

Paris, , France

Polyclinique Francheville

Périgueux, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Centre Hospitalier de La Region D'Annecy

Pringy, , France

Institut Curie - Centre Rene Huguenin

Saint-Cloud, , France

Ico - Centre Rene Gauducheau

Saint-Herblain, , France

CH de Senlis

Senlis, , France

Centre Paul Strauss

Strasbourg, , France

Hôpitaux du Léman

Thonon-les-Bains, , France

Institut Claudius Regaud

Toulouse, , France

Polyclinique Du Parc

Toulouse, , France

Clinique Saint Jean du Languedoc

Toulouse, , France

Clinique Pasteur

Toulouse, , France

Countries

France

Other Identifiers

GERICO10/0910 (GetugP03)

Identifier Type: -

Identifier Source: org_study_id