Sirolimus Before Surgery in Treating Patients With Advanced Localized Prostate Cancer

NCT00311623 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: J0576P30CA006973CDR0000468942NA_00001011
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This clinical trial is studying the best dose of sirolimus and to see how well it works before surgery in treating patients with advanced localized prostate cancer.

Conditions

Prostate Cancer

Keywords

stage III prostate cancer; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer; adenocarcinoma of the prostate

Outcome Measures

Primary Outcomes (3)

• Pharmocodynamically Optimal Dose (POD) of Rapamycin as Determined by Number of Participants With Greater Than or Equal to 60% Tumor S6 Kinase Inhibition by Immunohistochemistry (IHC).

  Day 15 post-intervention

• Median S6 Kinase Inhibition in Prostate Tumor Tissue at the POD

  Change from baseline to 15 days post-intervention

• Pharmacodynamic Response as Assessed by Median Post-treatment S6 Activity H-score

  Pharmocodynamic response was taken as ≥60% decrease in the H-score for S6 phosphorylation in the radical prostatectomy tumor tissue compared with the pretreatment (baseline) biopsy tumor tissue. The H-score is a semiquantitative measure of the percentage of cells scoring positive (0-100) multiplied by the intensity of staining (0-3).

  Change from baseline to 15 days post-intervention

Secondary Outcomes (10)

• Pharmacokinetic Response of Rapamycin 3mg as Assessed by Whole Blood Analysis

  Change from baseline to 15 days post-intervention

• Pharmacokinetic Response of Rapamycin 6mg as Assessed by Whole Blood Analysis

  Change from baseline to 15 days post-intervention

• Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC)

  Change from baseline to 15 days post-intervention

• PTEN Loss as Measured by Immunohistochemistry (IHC)

  Change from baseline to 15 days post-intervention

• p27 as Measured by Immunohistochemistry (IHC)

  Change from baseline to 15 days post-intervention

Study Arms (3)

Control group

ACTIVE COMPARATOR

Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy. Receive no intervention on Days 1-14. Surgery performed on Day 15.

Procedure: Radical prostatectomy

Low-dose Rapamycin (3mg)

EXPERIMENTAL

Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy. Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer. Will receive rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).

Drug: Rapamycin 3mg; Procedure: Radical prostatectomy

High-dose Rapamycin (6mg)

EXPERIMENTAL

Men \>18years old with prostate cancer clinical stages T1c to T3, no metastases, Gleason sum of 7-10, multiple positive diagnostic cores, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, candidates for radical prostatectomy. Must have adequate hepatic, renal and bone marrow function, no allergy to rapamycins, avoid medications interfering with rapamycin metabolism, no active infection, no prior therapies for prostate cancer. Will receive rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) oral (PO) once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).

Drug: Rapamycin 6mg; Procedure: Radical prostatectomy

Interventions

Rapamycin 3mg DRUG

Rapamycin 3mg (Wyeth Pharmaceuticals, 1mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).

Also known as: sirolimus

Low-dose Rapamycin (3mg)

Rapamycin 6mg DRUG

Rapamycin 6mg (Wyeth Pharmaceuticals, 2mg tablets) PO once daily on Days 1-14 with the last dose given on the morning before surgery (Day 15).

Also known as: sirolimus

High-dose Rapamycin (6mg)

Radical prostatectomy PROCEDURE

Radical prostatectomy performed on Day 15

Control group; High-dose Rapamycin (6mg); Low-dose Rapamycin (3mg)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically determined adenocarcinoma of the prostate * Stage T1c-T3b disease * No evidence of disease that has spread beyond the prostate or seminal vesicles * No metastatic prostate cancer, including bone, visceral, brain, and lymph node metastases * Tumor Gleason score sum of 7-10 (4+3 and 3+4 allowed) with tumor involving at least 2 discrete core biopsy sections * Scheduled to undergo radical prostatectomy * No other subtypes of prostate cancer, including any of the following: * Sarcoma * Neuroendocrine tumors * Small cell cancer * Ductal cancer * Lymphoma PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * WBC \> 3,500/mm\^3 * Absolute neutrophil count \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin \> 9 g/dL * Creatinine \< 2.0 mg/dL * Bilirubin \< 2 mg/dL * ALT and AST \< 2 times upper limit of normal (ULN) * Alkaline phosphatase \< 2 times ULN * Triglycerides and total cholesterol \< 2 times ULN * No history of allergy to sirolimus (rapamycin) or its derivatives * No uncontrolled medical condition that would increase risk or limit compliance with study requirements, including the following: * Immunodeficiency * Gastrointestinal disease that would limit ability to swallow, take oral medications, or absorb them * No active infections * No other concurrent malignancy PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy, biologic therapy, radiotherapy, or immunotherapy for prostate cancer * No concurrent chronic treatment with immunosuppressants or medications that interfere with the metabolism of sirolimus (rapamycin) * No concurrent medication or agents that would interfere with the metabolism or excretion of rapamycin or its derivatives, including any of the following: * Phenytoin * Carbamazepine * Cyclosporine * Clarithromycin * Clotrimazole * Erythromycin * Amiodarone * Protease inhibitors used to treated HIV infection * Cisapride * Grapefruit juice * Diltiazem * Tacrolimus * Hypericum perforatum (St. John's wort) * Barbiturates * Rifampin * Phenobarbital * Rifabutin * Efavirenz * Nevirapine * At least 7 days since prior herbal medicines and medications, including any of the following: * Hydrastis canadensis (goldenseal) * Uncaria tomentosa (cat's claw) * Echinacea angustifolia roots * Trifolium pretense (wild cherry) * Chamomile * Glycyrrhiza glabra (licorice) * Dillapiol * Naringenin * Norfloxacin * Atorvastatin * Pravastatin * Cimetidine * Fluconazole

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Armstrong AJ, Netto GJ, Rudek MA, Halabi S, Wood DP, Creel PA, Mundy K, Davis SL, Wang T, Albadine R, Schultz L, Partin AW, Jimeno A, Fedor H, Febbo PG, George DJ, Gurganus R, De Marzo AM, Carducci MA. A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer. Clin Cancer Res. 2010 Jun 1;16(11):3057-66. doi: 10.1158/1078-0432.CCR-10-0124. Epub 2010 May 25.

  PMID: 20501622 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Andrew Armstrong, MD ScM FACP
• Organization: Duke University

andrew.armstrong@duke.edu

(919) 668-8797

Study Officials

• Michael A. Carducci, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2006
• First Posted: April 6, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: June 1, 2010
• Last Updated: February 22, 2019
• Results First Posted: February 22, 2019

Record last verified: 2019-02

Locations

US (3)