Everolimus, Bicalutamide, and Leuprolide Acetate in Treating Patients Undergoing Radiation Therapy For High-Risk Locally Advanced Prostate Cancer

This study has been completed.
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier:
First received: July 21, 2009
Last updated: August 3, 2015
Last verified: August 2015

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide and leuprolide acetate may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with bicalutamide, leuprolide acetate, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with bicalutamide and leuprolide acetate in treating patients with high-risk locally advanced prostate cancer undergoing radiation therapy.

Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: everolimus
Drug: leuprolide acetate
Radiation: external beam radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial to Evaluate Acute and Late Toxicities of Concurrent Treatment With Everolimus (RAD001) and Radio-Hormonotherapy in High-risk Prostate Cancer.

Resource links provided by NLM:

Further study details as provided by Institut du Cancer de Montpellier - Val d'Aurelle:

Primary Outcome Measures:
  • Acute and late toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Biochemical-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Metastasis-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Pre-treatment molecular characteristics of the tumor and its correlation with outcomes [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Everolimus + radiation
Drug: bicalutamide Drug: everolimus Drug: leuprolide acetate Radiation: external beam radiation therapy

Detailed Description:



  • To assess acute and late toxicities in patients with high-risk, locally advanced prostate cancer.


  • To assess the biochemical-free survival of these patients.
  • To assess metastasis-free survival of these patients.
  • To assess the overall survival of these patients.
  • To assess the molecular characteristics of the tumor before treatment and correlate with outcomes.

OUTLINE: This is a dose-escalation study of everolimus.

Patients undergo radiotherapy to the prostate and seminal vesicles once daily, 5 days a week, for 7.5 weeks.

Beginning the week before radiotherapy, patients receive oral bicalutamide once daily for 1 month and oral everolimus twice daily for 8.5 weeks. Beginning on the first week of radiotherapy, patients receive leuprolide acetate subcutaneously every 3 months for 2 years.


Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • Diagnosis of high-risk, locally advanced prostate cancer meeting ≥ 1 of the following criteria:

    • Clinical stage ≥ T3
    • Gleason score ≥ 8
    • PSA ≥ 20 ng/mL
  • Previously untreated disease
  • Non-metastatic disease as assessed by bone scan and CT scan of the thorax and abdomen
  • Negative pelvic lymph nodes as proven by pathological analysis


  • WHO performance status 0-1
  • WBC ≥ 3.5 x 10^9/L
  • ANC ≥ 1.5 x 10^9/L
  • Platelets normal
  • Hemoglobin > 10 g/dL
  • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Albumin ≥ 3 g/dL
  • Serum transaminases activity ≤ 2.5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN
  • Covered by national health insurance
  • No history of previous malignant disease, except for adequately treated basal cell carcinoma of the skin
  • No ≥ grade 3 hypercholesterolemia/hypertriglyceridemia or ≥ grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment, if given)
  • No uncontrolled infection
  • No dysphagia or intestinal malabsorption
  • No other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes mellitus, uncontrolled cardiac disease [unstable angina], uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past six months, chronic liver or renal disease, and active upper gastrointestinal tract ulceration)
  • No history of noncompliance to medical regimens
  • No known hypersensitivity to everolimus, sirolimus (rapamycin), or temsirolimus
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study treatment and follow-up schedule


  • See Disease Characteristics
  • More than 30 days since prior investigational drugs
  • More than 10 days since prior and no concurrent treatment with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00943956

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Principal Investigator: David Azria, MD, PhD Institut du Cancer de Montpellier - Val d'Aurelle
  More Information

Additional Information:
No publications provided

Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT00943956     History of Changes
Other Study ID Numbers: CDR0000639358, CLCC-RHOMUS, CRAD001 C2486, INCA-RECF0921, EUDRACT-2007-003620-38
Study First Received: July 21, 2009
Last Updated: August 3, 2015
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Institut du Cancer de Montpellier - Val d'Aurelle:
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Androgen Antagonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2015