Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT00973882
First received: September 7, 2009
Last updated: November 2, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Carboplatin
Drug: Etoposide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation.

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response (clinical and/or biological) [ Time Frame: Every three months until progression ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Every 3 weeks during treatment ] [ Designated as safety issue: No ]
  • Progression-free survival and overall survival [ Time Frame: Every three months until progression ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2005
Study Completion Date: January 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carboplatin-Etoposide Drug: Carboplatin
Carboplatin AUC4 on day 1 repeated every 3 weeks for a maximum of 6 cycles
Drug: Etoposide
Etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00973882

Locations
France
Centre François Baclesse
Caen, France, 14021
Hôpital Henri Mondor
Créteil, France, 94000
Centre Georges François Leclerc
Dijon, France, 21000
Centre Hospitalier Départemental Les Oudairies
La Roche Sur Yon, France, 85925
Centre Leon Berard
Lyon, France, 69008
Institut Paoli Calmette
Marseille, France, 13273
Centre Val d'Aurelle
Montpellier, France, 34298
Institut Curie
Paris, France, 75005
Hopital Européen Georges Pompidou
Paris, France, 75908
Fondation Hôpital Saint-Joseph
Paris, France, 75674
Hopital Foch
SURESNES Cedex, France, 92151
Sponsors and Collaborators
Centre Leon Berard
Investigators
Principal Investigator: FLECHON Aude, MD Centre Leon Berard
  More Information

Publications:
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457-81, 1958

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT00973882     History of Changes
Other Study ID Numbers: CARBETOP, ET2005-005
Study First Received: September 7, 2009
Last Updated: November 2, 2011
Health Authority: France: Direction Générale de la Santé

Keywords provided by Centre Leon Berard:
Hormone resistant prostate cancer
Neuro-endocrine marker
Carboplatin-Etoposide combination
Neuro-endocrine differentiation

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Etoposide
Etoposide phosphate
Carboplatin
Hormones
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014