Clinical trial NCT01254513: Feasibility of a Chemotherapy With Docetaxel-Prednisone for Castration-resistant Metastatic Prostate Cancer Elderly Patients
Official title: Randomized Phase II Study Evaluating the Feasibility of a Chemotherapy With Docetaxel-Prednisone in a Weekly Schedule or Every 3 Weeks, for Castration-resistant Metastatic Prostate Cancer Elderly Patients (>=75), "Vulnerable" or "Frail" , as Defined by the Criteria of the International Society of Geriatric Oncology (SIOG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Metastatic Prostate cancer
Elderly patients
Vulnerable and Frail (SIOG classification)
castration-resistant
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2010-12-06
Enrollment: 66
Sex: MALE
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility of 2 different protocols of Docetaxel chemotherapy
timeFrame: Up to 18 weeks (6 cycles of chemotherapy)
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization until death for any cause or last follow-up news (censored data)
measure: Geriatric evaluation
timeFrame: At baseline, D1 of Cycle 1 and Cycle 4, at the end of treatment and at follow-up visits
measure: Number of patients with Adverse Events
timeFrame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits
measure: Quality of Life
timeFrame: At baseline, D1 of the Cycle 4, at the end of the treatment and at the follow-up visits
measure: Vital signs measurement
timeFrame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits
measure: Prostate-specific antigen (PSA) measurements
timeFrame: At baseline, D1 of each cycle , at the end of treatment and at the follow-up visits
Other outcomes:
Locations:
city: Albi
country: France
facility: Clinique Claude Bernard
city: Ambilly
country: France
facility: CHI Annemasse-Bonneville
city: Angers
country: France
facility: Centre Paul Papin
city: Blois
country: France
facility: CH de Blois
city: Bordeaux Cedex
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Castres
country: France
facility: CH Intercommunal
city: Chambery
country: France
facility: Centre Hospitalier de Chambery
city: Clermont-ferrand
country: France
facility: Centre Jean Perrin
city: Hyeres
country: France
facility: Clinique Sainte Marguerite
city: La Roche Sur Yon
country: France
facility: Chd Vendee
city: Levallois-perret
country: France
facility: Clinique Hartmann
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nimes
country: France
facility: CHU Nimes
city: Orleans
country: France
facility: Chr Orleans
city: Paris
country: France
facility: Institut Curie/Claudius Regaud
city: Pierre-benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Pringy Cedex
country: France
facility: Centre Hospitalier de La Region D'Annecy
city: Périgueux
country: France
facility: Polyclinique Francheville
city: Saint-cloud
country: France
facility: Institut Curie - Centre Rene Huguenin
city: Saint-herblain Cedex
country: France
facility: Ico - Centre Rene Gauducheau
city: Senlis
country: France
facility: CH de Senlis
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Thonon-les-bains
country: France
facility: Hôpitaux du Léman
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Toulouse
country: France
facility: Polyclinique Du Parc
city: Toulouse
country: France
facility: Clinique Saint Jean du Languedoc
city: Toulouse
country: France
facility: Clinique Pasteur
Study officials:
affiliation: Institut Claudius Regaud
name: Loic Mourey
role: PRINCIPAL_INVESTIGATOR
References: