Prostate CancerPhase 2NCT00460031
Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy
A Phase 2 study testing ketoconazole, lenalidomide and therapeutic hydrocortisone in people with Prostate Cancer, run by Case Comprehensive Cancer Center at 6 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- ketoconazole, lenalidomide and therapeutic hydrocortisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 Sep 2006to 31 Aug 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Lake/University Seidman Cancer Center
Cleveland, Ohio, 44060
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
University Suburban Health Center
Cleveland, Ohio, 44121
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, 44122
UHHS Westlake Medical Center
Cleveland, Ohio, 44145
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients With Prostate Cancer Progressive After Androgen Deprivation
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.
Read the detailed description
OBJECTIVES:
Primary
- Determine the objective response frequency in patients with hormone-refractory progressive prostate cancer treated with ketoconazole, hydrocortisone, and lenalidomide.
Secondary
- Determine the effect of this regimen on time to clinical progression in these patients.
- Determine the safety of this regimen in these patients.
- Determine the effects of this regimen on serum cytokines, including tumor necrosis factor-alpha, basic fibroblast growth factor, plasma soluble interleukin (IL)-2 receptor, IL-8, and IL-12, as well as serum vascular endothelial growth factor levels in these patients.
- Determine the co-stimulatory effects of this regimen on dendritic cells and CD4-positive, CD25-positive, T-regulatory cells in these patients.
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.
- Conditions
- Prostate Cancer
- Being tested
- ketoconazole, lenalidomide, therapeutic hydrocortisone
- Keywords
- adenocarcinoma of the prostate, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketoconazoleDrug
Also called held for toxicity, missed days of therapy are not made up.
400 tid
lenalidomideDrug
Lenalidomide will be administered daily at a dose of 25mg po qd on days 1-21 of the cycle.
therapeutic hydrocortisoneDrug
20mg qam 10mg qhs
| Study group | Role | What they receive |
|---|---|---|
| Ketoconazole Plus Lenalidomide | Experimental | Not described Receives: Drug: ketoconazole; Drug: lenalidomide; Drug: therapeutic hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2007 (estimated)
- Study start1 Sep 2006
- Primary completion31 Aug 2010
- Study completion31 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jorge Garcia, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterMatthew M. Cooney, MD, Principal investigator, University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00460031
- Sponsor's protocol ID
- CASE12805
- Status last verified
- Jul 2020
- First submitted
- 11 Apr 2007
- Last updated
- 24 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Barata PC, Cooney M, Mendiratta P, Tyler A, Dreicer R, Garcia JA. Ketoconazole plus Lenalidomide in patients with Castration-Resistant Prostate Cancer (CRPC): results of an open-label phase II study. Invest New Drugs. 2018 Dec;36(6):1085-1092. doi: 10.1007/s10637-018-0660-3. Epub 2018 Sep 6.
PubMed 30191523
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients With Prostate Cancer Progressive After Androgen Deprivation
- ClinicalTrials.gov ID
- NCT00460031
- Acronym / sponsor ID
- CASE12805
- Conditions
- Prostate Cancer
- Keywords
- adenocarcinoma of the prostate, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Sep 2006 (actual)
- Primary completion
- 31 Aug 2010 (actual)
- Study completion
- 31 Aug 2010 (actual)
- First posted
- 13 Apr 2007 (estimated)
- Results
- Posted 9 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- Determine the objective response frequency in patients with hormone-refractory progressive prostate cancer treated with ketoconazole, hydrocortisone, and lenalidomide.
Secondary
- Determine the effect of this regimen on time to clinical progression in these patients.
- Determine the safety of this regimen in these patients.
- Determine the effects of this regimen on serum cytokines, including tumor necrosis factor-alpha, basic fibroblast growth factor, plasma soluble interleukin (IL)-2 receptor, IL-8, and IL-12, as well as serum vascular endothelial growth factor levels in these patients.
- Determine the co-stimulatory effects of this regimen on dendritic cells and CD4-positive, CD25-positive, T-regulatory cells in these patients.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketoconazole Plus Lenalidomide | Experimental | Drug: ketoconazole, Drug: lenalidomide, Drug: therapeutic hydrocortisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ketoconazoleAlso: held for toxicity, missed days of therapy are not made up.400 tid | Drug | Ketoconazole Plus Lenalidomide |
| lenalidomideLenalidomide will be administered daily at a dose of 25mg po qd on days 1-21 of the cycle. | Drug | Ketoconazole Plus Lenalidomide |
| therapeutic hydrocortisone20mg qam 10mg qhs | Drug | Ketoconazole Plus Lenalidomide |
Primary outcome
Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease
Time frame: 28 days
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.
4 secondary outcomes
Time to Progression
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
Time frame: Up to 30 days after discontinuation of treatment
Change in Immune Response From Baseline
Time frame: Week 8
Ratio of Change in Immune Response From Baseline
Time frame: Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30191523Barata PC, Cooney M, Mendiratta P, Tyler A, Dreicer R, Garcia JA. Ketoconazole plus Lenalidomide in patients with Castration-Resistant Prostate Cancer (CRPC): results of an open-label phase II study. Invest New Drugs. 2018 Dec;36(6):1085-1092. doi: 10.1007/s10637-018-0660-3. Epub 2018 Sep 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge Garcia, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Matthew M. Cooney, MD principal investigator
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ketoconazole, lenalidomide and therapeutic hydrocortisone in people with Prostate Cancer, run by Case Comprehensive Cancer Center at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With a Partial Response, Progressive Disease, or Stable Disease Based on Prostate-Specific Antigen (PSA) or Measurable Disease (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00460031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.