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Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation.

Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation.

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.

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

- 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

- 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

- 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

- Symptomatically uncontrolled brain metastasis

- Interstitial radiation therapy (using strontium or samarium) within the previous 3

- 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

- Concomitant treatment with other anti-cancer drugs, except corticoid or LH-RH agonist

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome 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

Outcome Time Frame:

Every 6 weeks during treatment (6 cycles of carboplatin-etoposide) and 3 to 4 weeks after the end of treatment

Safety Issue:


Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Leon Berard


France: Direction Générale de la Santé

Study ID:




Start Date:

April 2005

Completion Date:

January 2010

Related Keywords:

  • Prostate Cancer
  • Hormone resistant prostate cancer
  • Neuro-endocrine marker
  • Carboplatin-Etoposide combination
  • Neuro-endocrine differentiation
  • Prostatic Neoplasms