Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

Phase 2

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: Carboplatin; Drug: Etoposide

• Registration Number: NCT00973882
• Lead Sponsor: Centre Leon Berard

Brief Summary

The aim of our study is to assess the efficacy and toxicity of a chemotherapy regimen combining carboplatin and etoposide in patients with metastatic hormone-resistant prostate cancer and neuro-endocrine differentiation. Eligible patients are treated with the combination of carboplatin AUC4 on day 1 and etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles. Efficacy endpoints include Prostate Specific Antigen (PSA) and neuro-endocrine marker response (defined as a 50% or greater decrease from baseline serum values), objective response rate (according to RECIST criteria), and toxicity.

Detailed Description

Neuro-endocrine differentiation is observed in the evolution of hormone-resistant prostate cancer. The aim of our study is to assess the efficacy and toxicity of a chemotherapy regimen combining carboplatin and etoposide in patients with metastatic hormone-resistant prostate cancer and neuro-endocrine differentiation. To be eligible, patients must have either circulating neuro-endocrine markers (Chromogranin A: CgA, Neuron Specific Enolase: NSE)and/or visceral metastases. Eligible patients are treated with the combination of carboplatin AUC4 administered on day 1 and etoposide 100 mg/m2 given on day 1, day 2 and day 3 and repeated every 3 weeks for a maximum of 6 cycles. The primary objective of the study is to assess objective response to the carboplatin - etoposide combination (according to RECIST criteria for lesions and defined as a 50% or greater decrease from baseline serum values for PSA and neuro-endocrine markers). Secondary objectives include evaluation of toxicity, duration of response, progression-free-survival and overall survival.

Study Timeline

• Study Start: 2005-04
• Primary Completion: 2009-07
• Study First Submitted: 2009-09-07
• Study First Submitted QC: 2009-09-08
• Study First Posted: 2009-09-09
• Study Completion: 2010-01
• Status Verified: 2011-11
• Last Update Submitted: 2011-11-02
• Last Update Posted: 2011-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 60

Inclusion Criteria

• Histological evidence of prostate adenocarcinoma

• Metastatic disease, either measurable (lymph nodes, hepatic lesion, pulmonary lesions with longest diameter > or = 1 cm on spiral scan), or non measurable (bone metastasis)

• Patients must:

  • Have received hormonal therapy via surgical or chemical castration (LH-RH agonist) with or without anti-androgens. Anti-androgen withdrawal is recommended before inclusion, with an off-treatment period of at least 4 weeks. LH-RH agonist treatment must be continued.

  • Have a relapse or disease refractory to hormonal treatment (defined by a testosterone level < 0.5 µg/ml)

  • Have neuroendocrine progression defined, whatever the PSA level, as:

    • NSE and/or Chromogranin A > 1.5 x upper limit of normal (ULN) with or without visceral metastases (liver, lung, lymph node)
    • No increase of NSE or Chromogranin A, but visceral metastases (either hepatic, pleuro-pulmonary, or nodal) with cytological or histological confirmation of the presence of an undifferentiated or neuro-endocrine component of prostatic origin

• Prior treatment by radiotherapy is allowed but radiation therapy must have been completed for at least 4 weeks before inclusion and irradiated areas must not represent more than 25% of marrow reserves

• Prior treatment by estramustine is allowed but must have been stopped at least 4 weeks before inclusion

• Age> or = 18 years

• Life expectancy> or = 3 months

• Karnofsky index> or = 50%

• Adequate haematological function: neutrophils> or = 1.5 G/l, platelets> or = 100 G/l, haemoglobin> or = 8 g/dl. Use of erythropoietin is allowed.

• Adequate liver function: bilirubin level within the institution's normal range, AST and ALT< or = 1.5 ULN

• Adequate renal function: creatinine clearance> or = 40 ml/min (Gault and Cockroft method)

• Signed written informed consent.

Exclusion Criteria

• Patients having no> 1.5 x ULN increase of at least one neuro-endocrine marker (NSE or chromogranin A) and no cytological or histological (undifferentiated or neuro-endocrine type) evidence of visceral metastasis (hepatic, pleuro-pulmonary, or nodal)
• History of other malignancies, other than curatively treated basal cell skin carcinoma or any other curatively treated cancer with no sign of recurrence within 5 years
• Symptomatically uncontrolled brain metastasis
• Interstitial radiation therapy (using strontium or samarium) within the previous 3 months
• Prior treatment with platinum salts or etoposide. Other chemotherapy regimens are allowed provided that the last dose has been administered> or = 4 weeks prior to inclusion.
• Concomitant treatment with other anti-cancer drugs, except corticoid or LH-RH agonist injections
• Peripheral neuropathy> or = 2 (NCI-CTCAE)
• Uncontrolled progressive thrombo-embolic disease
• Uncontrolled infection
• Medical history of acute myocardial infection or uncontrolled angina pectoris, or hypertension or uncontrolled arrythmia
• Inclusion in another clinical trial
• Impaired follow-up for social, geographical, familial or psychological reasons
• Any other unstable disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carboplatin-Etoposide	Carboplatin	-
Carboplatin-Etoposide	Etoposide	-

Primary Outcome Measures

Name	Time	Method
Objective response rate (clinical and/or biological): Clinical: objective response of target lesions according to RECIST criteria Biological: greater than 50% decrease of PSA, NSE and Chromogranin A levels	Every 6 weeks during treatment (6 cycles of carboplatin-etoposide) and 3 to 4 weeks after the end of treatment

Secondary Outcome Measures

Name	Time	Method
Duration of response (clinical and/or biological)	Every three months until progression
Toxicity	Every 3 weeks during treatment
Progression-free survival and overall survival	Every three months until progression

Trial Locations

Locations (11)

Centre Val d'Aurelle; 🇫🇷 Montpellier, France

Centre Leon Berard; 🇫🇷 Lyon, France

Centre François Baclesse; 🇫🇷 Caen, France

Fondation Hôpital Saint-Joseph; 🇫🇷 Paris, France

Institut Paoli Calmette; 🇫🇷 Marseille, France

Hopital Foch; 🇫🇷 SURESNES Cedex, France

Hôpital Henri Mondor; 🇫🇷 Créteil, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Hopital Européen Georges Pompidou; 🇫🇷 Paris, France

Centre Hospitalier Départemental Les Oudairies; 🇫🇷 La Roche Sur Yon, France

Institut Curie; 🇫🇷 Paris, France