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

Institut du Cancer de Montpellier - Val d'Aurelle

Status and phase

Completed

Phase 1

Conditions

Prostate Cancer

Treatments

Radiation: external beam radiation therapy

Drug: everolimus

Drug: bicalutamide

Drug: leuprolide acetate

Study type

Interventional

Funder types

Other

Identifiers

NCT00943956

CLCC-RHOMUS

CRAD001 C2486

EUDRACT-2007-003620-38

INCA-RECF0921

CDR0000639358

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

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

Secondary

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.

Enrollment

30 patients

Sex

Male

Ages

Under 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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