Safety and Efficacy Study of of Docetaxel vs Docetaxel Estramustine in Hormone Refractory Prostatic Cancer

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT00541281
First received: October 9, 2007
Last updated: October 26, 2009
Last verified: October 2009
  Purpose

we propose to randomize patients with hormone resistant prostate cancer between docetaxel/estramustine/prednisone and docetaxel/prednisone in a phase II study. The principal endpoint will be the efficacy in term of PSA response.


Condition Intervention Phase
Hormone Resistant Prostate Cancer
Metastatic Prostate Cancer
Drug: docetaxel
Drug: estramustine
Drug: prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase Ii Trial Of Weekly Docetaxel, Estramustine And Prednisone Versus Docetaxel And Prednisone In Patient With Hormone-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • To compare the efficacy of the association of Docetaxel and Estramustineand Prednisone versus Docetaxel and Prednisone in the treatment of hormone refractory prostate cancer in terms o PSA response [ Time Frame: within 30 days after end of treatment ]

Secondary Outcome Measures:
  • PSA response Time to PSA progression PSA response duration Event Progression-Free Survival Overall survival Palliative response (Pain) Safety Objective response measurable disease (RECIST) [ Time Frame: untill death occurs ]

Enrollment: 150
Study Start Date: December 2003
Study Completion Date: February 2006
Arms Assigned Interventions
Active Comparator: A
weekly docetaxel and prednisone
Drug: docetaxel
35mg/m² on day 2 and 9 (21days in a cycle)
Other Name: Taxotere
Drug: estramustine
140mg caps x3 bid from day 1to 5 and day 8 to 12 of each cycle
Other Name: estramustine phosphate
Drug: prednisone
2x5 mg a day
Other Names:
  • medrol
  • prednisone
Active Comparator: B
weekly docetaxel (35mg/m&) plus prednisone 10mg a day associated with estramustine form day 1to 5 and 8 to 12
Drug: docetaxel
35mg/m² on day 2 and 9 (21days in a cycle)
Other Name: Taxotere
Drug: prednisone
2x5 mg a day
Other Names:
  • medrol
  • prednisone

Detailed Description:

The addition of estramustine to other chemotherapeutic agents that affect microtubule function may improve their efficacy15, 16, 17, 18. A phase III trial compared vinblastine versus the combination of vinblastine plus estramustine as treatment for patients with hormone-refractory prostate cancer. They showed that the association of estramustine and vinblastine was superior to vinblastine alone for time to progression, PSA response and survival (Hudes et al., ASCO 2002). In addition, Berry et al. found that estramustine/paclitaxel improved PSA response rate but not overall survival compared with paclitaxel alone (Berry et al. ASCO2001).

Similar association has been studied with docetaxel. In a phase I trial combining docetaxel and estramustine19, 53% of patients reported a decrease in narcotic use and 63% experienced a PSA response. In another phase I trial, a reduction in PSA of 50% or more was observed in 14 of 17 patients (82%)20. In a phase II trial involving 35 patients, a PSA response was reported in 74% of the patients and objective response in 4 out of 7 patients with measurable disease21. Median survival 22 months in this last study. These studies as well as other support the combination of estramustine and docetaxel in the treatment of HRPC22, 23.

Recently, Oudard et al. competed a phase II randomized study comparing mitoxantrone/prednisone versus docetaxel/estramustine prednisone24. Docetaxel was given either weekly or every 3 weeks. Association of docetaxel/estramustine was found superior to mitoxantrone in term of PSA response, (67-63% versus 18%), clinical benefit (79-56% versus 41%) and survival (19.2 months versus 11.6 months). In addition, toxicities of these regimens were manageable and predictable. In this study, patients received 2 mgr of coumadin to prevent thromboembolic event due to estramustine and only 7 % of the patients had thrombosis. Other grade III & IV toxicities of the estramustine/docetaxel combination included neutropenia (37% in the 3-week regimen and 0 % in the weekly regimen) nausea/vomiting (2% in the 3-week regimen and 0 % in the weekly regimen), diarrhea (7% in the 3-week regimen and 0 % in the weekly regimen). No febrile neutropenia was observed.

Although these data support a role for chemotherapy combinations, such as estramustine and docetaxel, in the treatment of HRPC, further studies are needed to determine the relative contribution of estramustine to the efficacy of docetaxel/estramustine regimen. In this context, we propose to randomize patients with hormone resistant prostate cancer between docetaxel/estramustine/prednisone and docetaxel/prednisone in a phase II study. The principal endpoint will be the efficacy in term of PSA response. We chose to use the weekly regimen as described by Oudard since the toxicity of this regimen is well described and is easily manageable in our experience.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent prior to beginning protocol specific procedures.
  • 18 years
  • Histologically/cytologically proven prostate adenocarcinoma.
  • Documented metastatic prostate adenocarcinoma
  • Patients must have received prior hormonal therapy as defined below:
  • Castration by orchiectomy and/or LHRH agonists with or without
  • Antiandrogens
  • Other hormonal agents (e.g., ketoconazole, ...)
  • Testosterone level should be < 50 ng/dl in all patients (castrated level).
  • Respect of antiandrogen withdrawal period
  • No prior chemotherapy regimen at the exception of estramustine phosphate.
  • documented disease progression defined either (i) by PSA increase and/or (ii) imaging:
  • Prior radiation therapy (to less or equal than 25% of the bone marrow only) is allowed. At least 4 weeks must have elapsed since the completion of radiation therapy and the patient must have recovered from side effects.
  • Prior surgery is allowed. At least 4 weeks must have elapsed since the completion of surgery.
  • Life expectancy > 3 months.
  • ECOG performance status 0-2.
  • Normal cardiac function.

Exclusion Criteria:

  • Prior chemotherapy except estramustine phosphate.(2)
  • Prior isotope therapy
  • Prior radiotherapy to >25% of bone marrow
  • Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the patient has been disease-free for >5 years.
  • Known brain or leptomeningeal involvement.
  • Symptomatic peripheral neuropathy > grade 2
  • Other serious illness or medical condition
  • Concurrent treatment with other experimental drugs.
  • Treatment with any other anti-cancer therapy (except LHRH agonists)
  • Treatment with systemic corticosteroids used for reasons other than specified by the protocol must be stopped prior to the administration of docetaxel.
  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: NCT00541281

Locations
Belgium
St Pierre
Ottignies, Brabant Wallon, Belgium, 1340
Notre Dame et Reine Fabiola
Charleroi, Hainaut, Belgium, 6000
RHMS louis caty
Baudour, Belgium, 7331
Clinique Saint Luc
Bouge, Belgium, 5004
CHR Warquignies
Boussu, Belgium, 7300
Az klina
Brasschaat, Belgium, 2930
Parc Léopold
Brussels, Belgium, 1040
Cliniques Universitaires St luc
Bruxelles, Belgium, 1200
Hôpitaux IRIS Sud
Bruxelles, Belgium, 1050
Sint Nilolaus
Eupen, Belgium, 4700
Clinique St Joseph
Gilly, Belgium, 6000
Notre Dame de Grâce
Gosselies, Belgium, 6041
CH Jolimont Lobbes
La-Louvière, Belgium, 7100
St Joseph
Liège, Belgium, 4000
CHU Ambroise paré
Mons, Belgium, 7000
clinique Sainte Elisabeth
Namur, Belgium, 5000
Notre Dame
Tournai, Belgium, 7500
Clinique Universitaire de Mt Godinne
Yvoir, Belgium, 5004
Luxembourg
CHR Luxembourg
Luxembourg, Luxembourg, 1210
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sanofi
Investigators
Principal Investigator: Jean-Pascal Machiels, MD PHD Cliniques Universitaires St Luc
Principal Investigator: Joseph Kerger, MD Clinqiue Universitaire de Mont Godinne
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00541281     History of Changes
Other Study ID Numbers: UCL-ONCO 04-001
Study First Received: October 9, 2007
Last Updated: October 26, 2009
Health Authority: Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
prostate cancer
hormone resistant
metastatic
estramustine combine to docetaxel
randomized study

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Estramustine
Hormones
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 16, 2014