A Phase 2 interventional study of ketoconazole and lenalidomide in Prostate Cancer, sponsored by Case Comprehensive Cancer Center. Completed at 6 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-07-24.
Sponsored by Case Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as ketoconazole, may stop the adrenal glands from making androgens. Lenalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving ketoconazole and hydrocortisone together with lenalidomide may be an effective treatment for prostate cancer.
PURPOSE: This phase II trial is studying how well giving ketoconazole and hydrocortisone together with lenalidomide works in treating patients with prostate cancer that did not respond to hormone therapy.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a nonrandomized, open-label study.
Patients receive oral ketoconazole 3 times daily and oral hydrocortisone twice daily on days 1-28 and oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection periodically during study for evaluation of prostate cancer-specific immune response. Blood samples are assessed by serum analysis, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay techniques to detect and quantify different cytokines, antiangiogenic markers, dendritic cells, and specific T-regulatory cells.
After completion of study therapy, patients are followed at 30 days.
PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 34 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Case Comprehensive Cancer Center is the lead sponsor of 484 studies on the registry; 59 are open to participants now.
Of its 74 completed or terminated interventional studies of FDA-regulated products, 45 (61%) have results posted.
Counted across the registry records on this site, refreshed daily.
PATIENTS WITH PROSTATE CANCER PROGRESSIVE AFTER ANDROGEN DEPRIVATION Inclusion Criteria Understand and voluntarily sign an informed consent form. Age 18 years at the time of signing the informed consent form. Histologically confirmed adenocarcinoma of the prostate. Testosterone less than 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy. All previous cancer therapy, including radiation, and surgery, must have been discontinued at least 4 weeks prior to receive first dose of study drug.
Progressive disease after androgen deprivation.
Exclusion Criteria Prior systemic chemotherapy for hormone refractory prostate cancer. Prior neoadjuvant and adjuvant chemotherapy are allowed when completed at least 12 months prior to enrollment.
Prior ketoconazole, aminoglutethimide or corticosteroids for the treatment of progressive prostate cancer.
Prior immunotherapy including, but not limited to, vaccines, Thalidomide, and or Lenalidomide like agents.
Supplements or complementary medicines/botanicals are not permitted while on protocol therapy, except for any combination of the following:
conventional multivitamin supplements selenium lycopene soy supplements Patients should review the label with their doctor prior to enrollment, and discontinue disallowed agents prior to study enrollment Serious intercurrent infections or non-malignant medical illnesses including autoimmune disorders that are uncontrolled.
Psychiatric illnesses/social situations that would limit compliance with protocol requirements.
Evidence of CNS (brain or Leptomeningeal) metastases or large pleural/pericardial effusions.
Known contraindication to receive Ketoconazole or Lenalidomide Concurrent use of ketoconazole with statin compounds is absolutely contraindicated. Thus, patients receiving Statin drugs (fluvastatin, atorvastatin, and simvastatin) should discontinue them for at least 7 days before starting ketoconazole.
Patients taking astemizole, terfenadine, or cisapride, rifampin or isoniazid are not eligible, unless they agreed to completely discontinue those agents. In that case, any of these agents should be discontinued at least 7 days prior to start therapy with Ketoconazole.
Use of any other experimental drug or therapy within 28 days of baseline. Known hypersensitivity to thalidomide or its analogues. Any prior use of Lenalidomide. Known positive for HIV or infectious hepatitis, type A, B or C. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the breast.
Drug: ketoconazole · Drug: lenalidomide · Drug: therapeutic hydrocortisone
400 tid
Also known as: held for toxicity, missed days of therapy are not made up.
Lenalidomide will be administered daily at a dose of 25mg po qd on days 1-21 of the cycle.
20mg qam 10mg qhs
Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.
Time frame: 28 days
Time to Progression
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.
Time frame: One year (12 months) after start of treatment
Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0
Patients will be evaluated for toxicity every 2 weeks during the first cycle. Thereafter, evaluations will be done every 28 days or more frequently if clinically indicated.
Time frame: Up to 30 days after discontinuation of treatment
Change in Immune Response From Baseline
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the levels of CD4+ FoxP3+ Regulatory T cells
Time frame: Week 8
Ratio of Change in Immune Response From Baseline
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the ratio of BDCA-2 to BDCA-1 cells
Time frame: Week 8
Thirty seven (37) patients were screened from Cleveland Clinic and University Hospitals in the Cleveland area from February 2007 to April 2009.Three patients were not eligible.
| Milestone | Ketoconazole Plus Lenalidomide |
|---|---|
| Started | 34 |
| Completed | 23 |
| Not completed | 11 |
| Withdrew: Adverse event | 5 |
| Withdrew: Withdrawal by subject | 5 |
| Withdrew: Death | 1 |
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.
| participants | Ketoconazole Plus Lenalidomide |
|---|---|
| Partial Response | 7 |
| Progressive Disease | 7 |
| Stable Disease | 9 |
Patients will be evaluated for clinical benefit monthly with PSA values.Patients who are benefiting from treatment are eligible for additional cycles of treatment. Thereafter, therapy will continue until criteria for progressive disease are met. Response is based on the RECIST criteria from the National Cancer institute. Complete Response (CR) disappearance of all target lesions; Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions from baseline; Progressive Disease (PD) \>= increase in the sum of the longest diameter of target lesions from baseline; Stable Disease (SD) neither sufficient for partial response nor sufficient increase for progressive disease.
| Months | Ketoconazole Plus Lenalidomide |
|---|---|
| Time to Progression | 3 (-1.52 to 7.52) |
Patients will be evaluated for toxicity every 2 weeks during the first cycle. Thereafter, evaluations will be done every 28 days or more frequently if clinically indicated.
| participants | Ketoconazole Plus Lenalidomide |
|---|---|
| Number of Patients With Grade 3 and 4 Toxicity as Assessed by NCI CTCAE v3.0 | 19 |
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the levels of CD4+ FoxP3+ Regulatory T cells
| cells/ul | Ketoconazole Plus Lenalidomide |
|---|---|
| Change in Immune Response From Baseline | 0.18 ± 0.31 |
The pattern of immune response by assessing T cell and dendritic cell markers, specifically by measuring the ratio of BDCA-2 to BDCA-1 cells
| ratio | Ketoconazole Plus Lenalidomide |
|---|---|
| Ratio of Change in Immune Response From Baseline | -0.39 ± 1.44 |
Collected over 30 Days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketoconazole Plus Lenalidomide | — | 12/34 (35.3%) | 34/34 (100%) |
| Event | Ketoconazole Plus Lenalidomide |
|---|---|
| VomitingGastrointestinal disorders | 3/34 |
| HemoglobinBlood and lymphatic system disorders | 2/34 |
| Cardiovascular/GeneralCardiac disorders | 2/34 |
| Diarrhea patients without colostomyGastrointestinal disorders | 2/34 |
| Dizziness/lightheadednessNervous system disorders | 2/34 |
| Blood/Bone MarrowBlood and lymphatic system disorders | 1/34 |
| Cardiovascular/ArrhythmiaCardiac disorders | 1/34 |
| Cardiac-ischemia/infarctionCardiac disorders | 1/34 |
| EdemaGeneral disorders | 1/34 |
| CoagulationBlood and lymphatic system disorders | 1/34 |
| Event | Ketoconazole Plus Lenalidomide |
|---|---|
| "Fatigue (lethargy, malaise, asthenia)"General disorders | 27/34 |
| HemoglobinInvestigations | 18/34 |
| LymphopeniaInvestigations | 17/34 |
| Rash/desquamationSkin and subcutaneous tissue disorders | 16/34 |
| NauseaGastrointestinal disorders | 14/34 |
| HypocalcemiaMetabolism and nutrition disorders | 14/34 |
| PlateletsBlood and lymphatic system disorders | 13/34 |
| EdemaGeneral disorders | 13/34 |
| Alkaline phosphataseInvestigations | 13/34 |
| SGPT (ALT) (serum glutamic pyruvic transaminase)Investigations | 13/34 |
| Age, Customized(participants) | Ketoconazole Plus Lenalidomide |
|---|---|
| 40-49 years | 2 |
| 50-59 years | 5 |
| 60-69 years | 10 |
| 70-79 years | 11 |
| 80-89 years | 6 |
| Sex: Female, Male(Participants) | Ketoconazole Plus Lenalidomide |
|---|---|
| Female | 0 |
| Male | 34 |
| Ethnicity (NIH/OMB)(Participants) | Ketoconazole Plus Lenalidomide |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 33 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Ketoconazole Plus Lenalidomide |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 3 |
| White | 30 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Ketoconazole Plus Lenalidomide |
|---|---|
| United States | 34 |
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