Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

NCT ID: NCT00526591

Last Updated: 2018-12-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2011-08-31

Brief Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.

Detailed Description

OBJECTIVES:

Primary

• To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.
• To evaluate the safety and tolerability of this drug in these patients.

Secondary

• To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.
• To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
• Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.

Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).

After completion of study therapy, patients are followed at 6 weeks.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low-dose Everolimus Cohort

5mg Everolimus daily continuously for 8 weeks and conventional surgery

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week

conventional surgery

Intervention Type: PROCEDURE

Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

High-dose Everolimus Cohort

10mg Everolimus daily continuously for 8 weeks and conventional surgery

Group Type: ACTIVE_COMPARATOR

Everolimus

Intervention Type: DRUG

Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week

conventional surgery

Intervention Type: PROCEDURE

Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

Interventions

Everolimus

Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week

Intervention Type: DRUG

conventional surgery

Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).

Intervention Type: PROCEDURE

Other Intervention Names

RAD-001

Eligibility Criteria

Inclusion Criteria

• ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 8 g/dL
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN
• PT/PTT normal (no anticoagulants)
• No active unresolved infection
• No known HIV positivity
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy

Exclusion Criteria

• Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or temsirolimus) or to its excipients
• Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of everolimus, including any of the following:

• Ulcerative disease
• Uncontrolled nausea
• Vomiting
• Diarrhea
• Malabsorption syndrome
• Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer
• Uncontrolled concurrent illness including, but not limited to, any of the following:

• Ongoing or active infection (e.g., bacterial, viral or fungal)
• Severely impaired lung function
• Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)
• Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would limit study compliance
• Any underlying medical condition which, in the principal investigator's opinion, will make the administration of everolimus hazardous OR obscure the interpretation of adverse events

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since major surgery
• More than 3 months since finasteride
• No prior or concurrent radiotherapy to the prostate gland or pelvis
• No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or PC-SPES (or PC-x product) or estrogen-containing nutraceuticals
• No prior rapamycin mTOR inhibitor
• No prior small bowel resection that may significantly impair GI function and alter the absorption of everolimus
• No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy for prostate cancer
• No other concurrent investigational or commercial agents
• No other concurrent anticancer agents
• No concurrent, chronic treatment with systemic steroids (except inhaled or topical steroids) or another immunosuppressive agent
• No concurrent live vaccines
• No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as systemic therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Jorge A. Garcia, MD

OTHER

Sponsor Role: lead

Responsible Party

Jorge A. Garcia, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jorge A. Garcia, MD

Role: PRINCIPAL_INVESTIGATOR

Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

Koshkin VS, Mir MC, Barata P, Gul A, Gupta R, Stephenson AJ, Kaouk J, Berglund R, Magi-Galluzzi C, Klein EA, Dreicer R, Garcia JA. Randomized phase II trial of neoadjuvant everolimus in patients with high-risk localized prostate cancer. Invest New Drugs. 2019 Jun;37(3):559-566. doi: 10.1007/s10637-019-00778-4. Epub 2019 Apr 30.

Reference Type: DERIVED

PMID: 31037562 (View on PubMed)

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-21806

Identifier Type: OTHER

Identifier Source: secondary_id

CASE-21806-CC256

Identifier Type: OTHER

Identifier Source: secondary_id

CASE21806

Identifier Type: -

Identifier Source: org_study_id