Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer

NCT01642732 | Terminated Phase 1 Results DMC

• 2 other identifiers: UMCC 2011.008HUM00047650
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

The purposes of this study are to:

• Determine the safest and highest dose of the study drug RAD001 (Everolimus) that can be taken in combination with hormonal and radiation therapy in men with high risk prostate cancer.
• Evaluate changes in patient reported quality of life
• Evaluate biomarkers from prostate tumor samples. Biomarkers are various traits which can be used to identify the progress of a disease or condition, which can help researchers determine the effect the study treatment has on the tumor. Biomarkers can also help determine areas for further research.

Conditions

Prostate Cancer

Keywords

Prostate; Cancer; Everolimus; Radiation

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Adverse Events on Oral Everolimus in Combination With Hormonal Ablation and External Beam Radiation

  64 months after beginning everolimus

Secondary Outcomes (1)

• Difference in Serologic Everolimus and Prostate Biomarker Levels Before and After Treatment With Everolimus

  Prior to treatment and at 14 days

Study Arms (1)

Everolimus with combined hormonal and radiation therapy

EXPERIMENTAL

Everolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1. Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks). Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy. Lupron injections will begin on study day 10 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections. Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study.

Other: Everolimus, lupron, bicalutamide, and radiation

Interventions

Everolimus, lupron, bicalutamide, and radiation OTHER

Everolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1. Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks). Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy. Lupron injections will begin on study day 15 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections. Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study.

Also known as: afinitor, RAD-001, Casodex, Leuprolide, Eligard

Everolimus with combined hormonal and radiation therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Participants must be able to care for themselves
• Adequate function
• Adequate kidney function
• Histologically confirmed diagnosis of adenocarcinoma of the prostate with biopsy within 90 days of enrollment
• High-risk prostate cancer
• No distant metastases as evaluated by a bone scan and CT of the pelvis (within 90 days of enrollment)
• Participants must have at least 4 biopsy cores containing prostate cancer with tissue available for histologic analysis
• Signed informed consent

You may not qualify if:

• Participants currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, targeted therapy, etc.)
• Prior pharmacologic androgen ablation for prostate cancer is not allowed including LHRH agonist therapy or oral anti-androgen therapy.
• o Previous use of either finasteride or dutasteride is allowed
• Participants, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or participants that may require major surgery during the course of the study
• Any previous therapeutic radiation therapy to the pelvis.
• Known gastrointestinal dysfunction or an inability to take oral medications that would preclude taking an oral medication.
• Prior treatment with any investigational drug within the preceding 4 weeks of registration
• Participants receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.
• o Topical or inhaled corticosteroids are allowed.
• Participants should not receive immunization with attenuated live vaccines within one week of registration or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
• Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin.
• Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• Uncontrolled cardiac arrhythmia
• The use of anti-arrhythmic medications or implanted pacemakers or defibrillators is allowed and would not exclude a patient from enrollment.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasms

Interventions

Everolimus; Leuprolide; bicalutamide; Radiation; luprolide acetate gel depot

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Physical Phenomena

Limitations and Caveats

Only one patient was enrolled to the trial and consent was withdrawn prior to treatment therefore the primary objective could not be analyzed.

Results Point of Contact

• Title: Dr. Daniel Hamstra, Associate Professor of Radiation Oncology
• Organization: University of Michigan Hospital

dhamm@umich.edu

734-936-4300

Study Officials

• Daniel A. Hamstra, M.D., Ph.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2012
• First Posted: July 17, 2012
• Study Start: October 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: November 20, 2014

Record last verified: 2017-05

Locations

US (2)