Clinical trial NCT00973882: Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers
Official title: Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Hormone resistant prostate cancer
Neuro-endocrine marker
Carboplatin-Etoposide combination
Neuro-endocrine differentiation
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2009-09-09
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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
* 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.

Primary outcomes:
measure: 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
timeFrame: Every 6 weeks during treatment (6 cycles of carboplatin-etoposide) and 3 to 4 weeks after the end of treatment
Secondary outcomes:
measure: Duration of response (clinical and/or biological)
timeFrame: Every three months until progression
measure: Toxicity
timeFrame: Every 3 weeks during treatment
measure: Progression-free survival and overall survival
timeFrame: Every three months until progression
Other outcomes:
Locations:
city: Caen
country: France
facility: Centre François Baclesse
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Départemental Les Oudairies
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Montpellier
country: France
facility: Centre Val d'Aurelle
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Fondation Hôpital Saint-Joseph
city: Paris
country: France
facility: Hopital Européen Georges Pompidou
city: SURESNES Cedex
country: France
facility: Hopital Foch
Study officials:
affiliation: Centre Leon Berard
name: FLECHON Aude, MD
role: PRINCIPAL_INVESTIGATOR
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