Prostate Cancer
Conditions
Keywords
Hormone resistant prostate cancer, Neuro-endocrine marker, Carboplatin-Etoposide combination, Neuro-endocrine differentiation
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.
Interventions
DRUGCarboplatin
Carboplatin AUC4 on day 1 repeated every 3 weeks for a maximum of 6 cycles
DRUGEtoposide
Etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles
Sponsors
Centre Leon Berard
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Progression-free survival and overall survival | Every three months until progression |
| Duration of response (clinical and/or biological) | Every three months until progression |
| Toxicity | Every 3 weeks during treatment |
Countries
France
Outcome results
None listed