Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation.
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Prostate Cancer
- Sponsor
- Centre Leon Berard
- Enrollment
- 60
- Locations
- 11
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 14 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Carboplatin-Etoposide
Intervention: Carboplatin
Carboplatin-Etoposide
Intervention: Etoposide
Outcomes
Primary Outcomes
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
Time Frame: Every 6 weeks during treatment (6 cycles of carboplatin-etoposide) and 3 to 4 weeks after the end of treatment
Secondary Outcomes
- 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)