Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

L

Léon Bérard Center

Status and phase

Completed
Phase 2

Conditions

Prostate Cancer

Treatments

Drug: Etoposide
Drug: Carboplatin

Study type

Interventional

Funder types

Other

Identifiers

NCT00973882
CARBETOP
ET2005-005

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

60 participants in 1 patient group

Carboplatin-Etoposide
Experimental group
Treatment:
Drug: Carboplatin
Drug: Etoposide

Trial contacts and locations

11

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems