Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Carboplatin-Etoposide
|
Drug: Carboplatin
Carboplatin AUC4 on day 1 repeated every 3 weeks for a maximum of 6 cycles
Drug: Etoposide
Etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histological evidence of prostate adenocarcinoma
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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:
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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.
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Have a relapse or disease refractory to hormonal treatment (defined by a testosterone level < 0.5 µg/ml)
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Have neuroendocrine progression defined, whatever the PSA level, as:
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NSE and/or Chromogranin A > 1.5 x upper limit of normal (ULN) with or without visceral metastases (liver, lung, lymph node)
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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
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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
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Prior treatment by estramustine is allowed but must have been stopped at least 4 weeks before inclusion
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Age> or = 18 years
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Life expectancy> or = 3 months
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Karnofsky index> or = 50%
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Adequate haematological function: neutrophils> or = 1.5 G/l, platelets> or = 100 G/l, haemoglobin> or = 8 g/dl. Use of erythropoietin is allowed.
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Adequate liver function: bilirubin level within the institution's normal range, AST and ALT< or = 1.5 ULN
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Adequate renal function: creatinine clearance> or = 40 ml/min (Gault and Cockroft method)
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Signed written informed consent.
Exclusion Criteria:
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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)
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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
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Symptomatically uncontrolled brain metastasis
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Interstitial radiation therapy (using strontium or samarium) within the previous 3 months
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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.
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Concomitant treatment with other anti-cancer drugs, except corticoid or LH-RH agonist injections
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Peripheral neuropathy> or = 2 (NCI-CTCAE)
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Uncontrolled progressive thrombo-embolic disease
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Uncontrolled infection
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Medical history of acute myocardial infection or uncontrolled angina pectoris, or hypertension or uncontrolled arrythmia
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Inclusion in another clinical trial
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Impaired follow-up for social, geographical, familial or psychological reasons
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Any other unstable disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre François Baclesse | Caen | France | 14021 | |
| 2 | Hôpital Henri Mondor | Créteil | France | 94000 | |
| 3 | Centre Georges François Leclerc | Dijon | France | 21000 | |
| 4 | Centre Hospitalier Départemental Les Oudairies | La Roche Sur Yon | France | 85925 | |
| 5 | Centre Leon Berard | Lyon | France | 69008 | |
| 6 | Institut Paoli Calmette | Marseille | France | 13273 | |
| 7 | Centre Val d'Aurelle | Montpellier | France | 34298 | |
| 8 | Institut Curie | Paris | France | 75005 | |
| 9 | Fondation Hôpital Saint-Joseph | Paris | France | 75674 | |
| 10 | Hopital Européen Georges Pompidou | Paris | France | 75908 | |
| 11 | Hopital Foch | SURESNES Cedex | France | 92151 |
Sponsors and Collaborators
- Centre Leon Berard
Investigators
- Principal Investigator: FLECHON Aude, MD, Centre Leon Berard
Study Documents (Full-Text)
None provided.More Information
Publications
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- Aumüller G, Leonhardt M, Janssen M, Konrad L, Bjartell A, Abrahamsson PA. Neurogenic origin of human prostate endocrine cells. Urology. 1999 May;53(5):1041-8.
- Bonkhoff H, Stein U, Remberger K. Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol. 1995 Feb;26(2):167-70.
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