Phase 2
Completed N=32
Sirolimus Before Surgery in Treating Patients With Advanced Localized Prostate Cancer
Source: ClinicalTrials.gov NCT00311623 ↗Enrolled (actual)
32
Serious AEs
6.3%
Results posted
Feb 2019
Primary outcomePrimary: 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). — 1; 5 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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). |
1; 5 | — |
| PRIMARY Median S6 Kinase Inhibition in Prostate Tumor Tissue at the POD |
2; 58 | — |
| PRIMARY Pharmacodynamic Response as Assessed by Median Post-treatment S6 Activity H-score |
140; 70 | — |
| SECONDARY Pharmacokinetic Response of Rapamycin 3mg as Assessed by Whole Blood Analysis |
— | — |
| SECONDARY Pharmacokinetic Response of Rapamycin 6mg as Assessed by Whole Blood Analysis |
— | — |
| SECONDARY Number of Participants With Change in Akt Phosphorylation as Measured by Immunohistochemistry (IHC) |
3; 4; 3; 4; 1; 2 | — |
| SECONDARY PTEN Loss as Measured by Immunohistochemistry (IHC) |
— | — |
| SECONDARY p27 as Measured by Immunohistochemistry (IHC) |
— | — |
| SECONDARY Change in Gleason Sum |
— | — |
| SECONDARY Increased Apoptosis as Measured by Activated Caspase 3 |
— | — |
| SECONDARY Reduction in Proliferation as Measured by Decrease in Ki-67 |
— | — |
| SECONDARY Toxicity as Per National Cancer Institute Common Toxicity Criteria v3.0 |
— | — |
| SECONDARY Activity of Rapamycin as Measured by Prostate Specific Antigen (PSA) Response Prior to Surgery |
— | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT00311623). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.