Carboplatin-Etoposide Combination in Hormone-Resistant Prostate Cancers

NCT ID: NCT00973882

Last Updated: 2011-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2010-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Prostate Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Carboplatin-Etoposide

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

Carboplatin AUC4 on day 1 repeated every 3 weeks for a maximum of 6 cycles

Etoposide

Intervention Type DRUG

Etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Carboplatin

Carboplatin AUC4 on day 1 repeated every 3 weeks for a maximum of 6 cycles

Intervention Type DRUG

Etoposide

Etoposide 100 mg/m2 on day 1, day 2 and day 3 repeated every 3 weeks for a maximum of 6 cycles

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Centre Leon Berard

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

FLECHON Aude, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Centre François Baclesse

Caen, , France

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Institut Paoli Calmette

Marseille, , France

Site Status

Centre Val d'Aurelle

Montpellier, , France

Site Status

Institut Curie

Paris, , France

Site Status

Fondation Hôpital Saint-Joseph

Paris, , France

Site Status

Hopital Européen Georges Pompidou

Paris, , France

Site Status

Hopital Foch

Suresnes, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

Aumuller G, Leonhardt M, Janssen M, Konrad L, Bjartell A, Abrahamsson PA. Neurogenic origin of human prostate endocrine cells. Urology. 1999 May;53(5):1041-8. doi: 10.1016/s0090-4295(98)00631-1.

Reference Type BACKGROUND
PMID: 10223503 (View on PubMed)

Bonkhoff H, Stein U, Remberger K. Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol. 1995 Feb;26(2):167-70. doi: 10.1016/0046-8177(95)90033-0.

Reference Type BACKGROUND
PMID: 7532147 (View on PubMed)

Krijnen JL, Janssen PJ, Ruizeveld de Winter JA, van Krimpen H, Schroder FH, van der Kwast TH. Do neuroendocrine cells in human prostate cancer express androgen receptor? Histochemistry. 1993 Nov;100(5):393-8. doi: 10.1007/BF00268938.

Reference Type BACKGROUND
PMID: 8307781 (View on PubMed)

Hansson J, Abrahamsson PA. Neuroendocrine pathogenesis in adenocarcinoma of the prostate. Ann Oncol. 2001;12 Suppl 2:S145-52. doi: 10.1093/annonc/12.suppl_2.s145.

Reference Type BACKGROUND
PMID: 11762343 (View on PubMed)

Abrahamsson PA. Neuroendocrine differentiation in prostatic carcinoma. Prostate. 1999 May;39(2):135-48. doi: 10.1002/(sici)1097-0045(19990501)39:23.0.co;2-s.

Reference Type BACKGROUND
PMID: 10221570 (View on PubMed)

Oesterling JE, Hauzeur CG, Farrow GM. Small cell anaplastic carcinoma of the prostate: a clinical, pathological and immunohistological study of 27 patients. J Urol. 1992 Mar;147(3 Pt 2):804-7. doi: 10.1016/s0022-5347(17)37390-1.

Reference Type BACKGROUND
PMID: 1311395 (View on PubMed)

Kreis W. Current chemotherapy and future directions in research for the treatment of advanced hormone-refractory prostate cancer. Cancer Invest. 1995;13(3):296-312. doi: 10.3109/07357909509094465. No abstract available.

Reference Type BACKGROUND
PMID: 7743383 (View on PubMed)

Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. doi: 10.1200/JCO.1996.14.6.1756.

Reference Type BACKGROUND
PMID: 8656243 (View on PubMed)

Moore MJ, Osoba D, Murphy K, Tannock IF, Armitage A, Findlay B, Coppin C, Neville A, Venner P, Wilson J. Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer. J Clin Oncol. 1994 Apr;12(4):689-94. doi: 10.1200/JCO.1994.12.4.689.

Reference Type BACKGROUND
PMID: 7512127 (View on PubMed)

Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748-56. doi: 10.1200/JCO.1989.7.11.1748.

Reference Type BACKGROUND
PMID: 2681557 (View on PubMed)

Chatelut E, Canal P, Brunner V, Chevreau C, Pujol A, Boneu A, Roche H, Houin G, Bugat R. Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst. 1995 Apr 19;87(8):573-80. doi: 10.1093/jnci/87.8.573.

Reference Type BACKGROUND
PMID: 7752255 (View on PubMed)

Maksymiuk AW, Jett JR, Earle JD, Su JQ, Diegert FA, Mailliard JA, Kardinal CG, Krook JE, Veeder MH, Wiesenfeld M, et al. Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial. J Clin Oncol. 1994 Jan;12(1):70-6. doi: 10.1200/JCO.1994.12.1.70.

Reference Type BACKGROUND
PMID: 8270988 (View on PubMed)

Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. doi: 10.1200/JCO.1995.13.10.2594.

Reference Type BACKGROUND
PMID: 7595712 (View on PubMed)

Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. doi: 10.1200/JCO.1995.13.8.1871.

Reference Type BACKGROUND
PMID: 7636529 (View on PubMed)

Larive S, Bombaron P, Riou R, Fournel P, Perol M, Lena H, Dussopt C, Philip-Joet F, Touraine F, Lecaer H, Souquet PJ; Groupe Lyon-Saint Etienne d'Oncologie Thoracique. Carboplatin-etoposide combination in small cell lung cancer patients older than 70 years: a phase II trial. Lung Cancer. 2002 Jan;35(1):1-7. doi: 10.1016/s0169-5002(01)00288-4.

Reference Type BACKGROUND
PMID: 11750705 (View on PubMed)

Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. doi: 10.1200/JCO.1999.17.11.3540.

Reference Type BACKGROUND
PMID: 10550152 (View on PubMed)

Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coetmeur D, Lemarie E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. doi: 10.1023/a:1011171722175.

Reference Type BACKGROUND
PMID: 11521802 (View on PubMed)

Papandreou CN, Daliani DD, Thall PF, Tu SM, Wang X, Reyes A, Troncoso P, Logothetis CJ. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol. 2002 Jul 15;20(14):3072-80. doi: 10.1200/JCO.2002.12.065.

Reference Type BACKGROUND
PMID: 12118020 (View on PubMed)

Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

Reference Type BACKGROUND
PMID: 2702835 (View on PubMed)

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

Reference Type BACKGROUND

Flechon A, Pouessel D, Ferlay C, Perol D, Beuzeboc P, Gravis G, Joly F, Oudard S, Deplanque G, Zanetta S, Fargeot P, Priou F, Droz JP, Culine S. Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial. Ann Oncol. 2011 Nov;22(11):2476-2481. doi: 10.1093/annonc/mdr004. Epub 2011 Mar 24.

Reference Type RESULT
PMID: 21436186 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ET2005-005

Identifier Type: -

Identifier Source: secondary_id

CARBETOP

Identifier Type: -

Identifier Source: org_study_id