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

Information source: University of Michigan Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prostate Cancer

Intervention: Everolimus, lupron, bicalutamide, and radiation (Other)

Phase: Phase 1

Status: Terminated

Sponsored by: University of Michigan Cancer Center

Official(s) and/or principal investigator(s):
Daniel A. Hamstra, M.D., Ph.D., Principal Investigator, Affiliation: University of Michigan Cancer Center

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.

Clinical Details

Official title: A Multi-institutional Phase I and Biomarker Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome: Correlation of Prostate Biomarkers With Serologic Everolimus Levels as Well as Changes From Pre- to Post-everolimus Will be Completed.

Detailed description: Prostate cancer is very prevalent with an estimated > 200,000 new cases and > 25,000 deaths attributable to prostate cancer in the United States in 2010. Radiation treatment represents a commonly utilized method to treat prostate cancer with an excellent chance of controlling disease with biochemical control at 5-years in excess of 75% in men with locally confined but intermediate to high-risk disease. However, despite impressive biochemical control, local control remains a problem. Everolimus is being investigated as an anticancer agent based on its potential to act:

- Directly on the tumor cells by inhibiting tumor cell growth and proliferation

- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity.

Given the prevalence of PTEN deletion in high-risk prostate cancers as well as the evidence that tumor hypoxia leads to increased risks of failure after treatment with hormonal therapy and radiation, we hypothesis that inhibition of mTOR signaling in both tumor and vascular cells using everolimus concurrent with hormonal and radiation therapy will enhance the efficacy of radiation therapy without an unacceptable risk of toxicity in men with high-risk prostate cancer. Everolimus has not been approved by the FDA for the treatment of prostate cancer by itself or in combination with radiation and hormonal therapy. It is not known if this combination is safe and effective in prostate cancer. The FDA has allowed their combined use in this clinical trial.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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.

- Unstable angina pectoris, symptomatic congestive heart failure, myocardial

infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease

- Severely impaired lung function

- Uncontrolled diabetes

- Active (acute or chronic) or uncontrolled severe infections

- Liver disease such as cirrhosis or severe hepatic impairment

- Uncontrolled diabetes mellitus despite adequate therapy. Patients with a known

history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary;

- A detailed assessment of Hepatitis B/C medical history and risk factors must be done

at screening for all participants.

- Participants with previous documented history of Hepatitis B/C infection are

excluded from enrollment.

- Participants with high risk for hepatitis based upon medical history and risk

factors must be screened for Hepatitis B and C, and if positive are excluded from enrollment.

- A known history of HIV seropositivity

- Participants with an active, bleeding diathesis

- Male patient whose sexual partner(s) are women of child bearing potential who are not

willing to use adequate contraception, during the study and for 8 weeks after the end of treatment

- Participants who have received prior treatment with an mTOR inhibitor (e. g.,

sirolimus, temsirolimus, everolimus). o Sirolimus eluting coronary artery stents are allowed

- Participants with a known hypersensitivity to everolimus or other rapamycins (e. g.,

sirolimus, temsirolimus) or to its excipients

- Participants unwilling to or unable to comply with the protocol

Locations and Contacts

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

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, United States

Additional Information

Starting date: October 2012
Last updated: November 13, 2014

Page last updated: August 23, 2015

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