Prostate CancerPhase 1NCT01642732
Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer
A Phase 1 study testing Everolimus, lupron, bicalutamide, and radiation in people with Prostate Cancer, run by University of Michigan Rogel Cancer Center at 2 sites in United States.
Trial summary
The purposes of this study are to: Determine the safest and highest dose of the study drug RAD001 (Everolimus) that can be taken in combination with hormonal and radiation therapy in men with high risk prostate cancer. 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?
- Everolimus, lupron, bicalutamide, and radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2012to Aug 2014
- Phase
- Phase 1
- 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
Who may be able to join
- Age ≥ 18 years
- Participants must be able to care for themselves
- Adequate function
- Adequate kidney function
- Histologically confirmed diagnosis of adenocarcinoma of the prostate with biopsy within 90 days of enrollment
- High-risk prostate cancer
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- No distant metastases as evaluated by a bone scan and CT of the pelvis (within 90 days of enrollment)
- Participants must have at least 4 biopsy cores containing prostate cancer with tissue available for histologic analysis
- Signed informed consent
Who cannot join
- Participants currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, targeted therapy, etc.)
- Prior pharmacologic androgen ablation for prostate cancer is not allowed including LHRH agonist therapy or oral anti-androgen therapy.
- o Previous use of either finasteride or dutasteride is allowed
- Participants, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or participants that may require major surgery during the course of the study
- Any previous therapeutic radiation therapy to the pelvis.
- Known gastrointestinal dysfunction or an inability to take oral medications that would preclude taking an oral medication.
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- Prior treatment with any investigational drug within the preceding 4 weeks of registration
- Participants receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.
- o Topical or inhaled corticosteroids are allowed.
- Participants should not receive immunization with attenuated live vaccines within one week of registration or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
- Other malignancies within the past 3 years except for adequately treated basal or squamous cell carcinomas of the skin.
- Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- Uncontrolled cardiac arrhythmia
- The use of anti-arrhythmic medications or implanted pacemakers or defibrillators is allowed and would not exclude a patient from enrollment.
- Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- Severely impaired lung function
- Uncontrolled diabetes
- Active (acute or chronic) or uncontrolled severe infections
- Liver disease such as cirrhosis or severe hepatic impairment
- Uncontrolled diabetes mellitus despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary;
- A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all participants.
- Participants with previous documented history of Hepatitis B/C infection are excluded from enrollment.
- Participants with high risk for hepatitis based upon medical history and risk factors must be screened for Hepatitis B and C, and if positive are excluded from enrollment.
- A known history of HIV seropositivity
- Participants with an active, bleeding diathesis
- Male patient whose sexual partner(s) are women of child bearing potential who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
- Participants who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
- o Sirolimus eluting coronary artery stents are allowed
- Participants with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
- Participants unwilling to or unable to comply with the protocol
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Georgetown University
Washington D.C., District of Columbia, 20057
About this study
Official title: A Multi-institutional Phase I and Biomarker Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer
The purposes of this study are to:
- Determine the safest and highest dose of the study drug RAD001 (Everolimus) that can be taken in combination with hormonal and radiation therapy in men with high risk prostate cancer.
- Evaluate changes in patient reported quality of life
- Evaluate biomarkers from prostate tumor samples. Biomarkers are various traits which can be used to identify the progress of a disease or condition, which can help researchers determine the effect the study treatment has on the tumor. Biomarkers can also help determine areas for further research.
Read the detailed description
Prostate cancer is very prevalent with an estimated > 200,000 new cases and > 25,000 deaths attributable to prostate cancer in the United States in 2010. Radiation treatment represents a commonly utilized method to treat prostate cancer with an excellent chance of controlling disease with biochemical control at 5-years in excess of 75% in men with locally confined but intermediate to high-risk disease. However, despite impressive biochemical control, local control remains a problem.
Everolimus is being investigated as an anticancer agent based on its potential to act:
- Directly on the tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity.
Given the prevalence of PTEN deletion in high-risk prostate cancers as well as the evidence that tumor hypoxia leads to increased risks of failure after treatment with hormonal therapy and radiation, we hypothesis that inhibition of mTOR signaling in both tumor and vascular cells using everolimus concurrent with hormonal and radiation therapy will enhance the efficacy of radiation therapy without an unacceptable risk of toxicity in men with high-risk prostate cancer.
Everolimus has not been approved by the FDA for the treatment of prostate cancer by itself or in combination with radiation and hormonal therapy. It is not known if this combination is safe and effective in prostate cancer. The FDA has allowed their combined use in this clinical trial.
- Conditions
- Prostate Cancer
- Being tested
- Everolimus, lupron, bicalutamide, and radiation
- Keywords
- Prostate, Cancer, Everolimus, Radiation
- Medical subject headings
- Prostatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus, lupron, bicalutamide, and radiationOther
Also called afinitor, RAD-001, Casodex, Leuprolide
Everolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1.
Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks).
Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy.
Lupron injections will begin on study day 15 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections.
Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus with combined hormonal and radiation therapy | Experimental | Everolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1.
Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks).
Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy.
Lupron injections will begin on study day 10 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections.
Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study. Receives: Other: Everolimus, lupron, bicalutamide, and radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Adverse Events on Oral Everolimus in Combination With Hormonal Ablation and External Beam Radiation
Measured: 64 months after beginning everolimus
Secondary outcomes (1)
Difference in Serologic Everolimus and Prostate Biomarker Levels Before and After Treatment With Everolimus
Analysis of pairs of markers will be explored looking for large positive or negative correlations to indicate marker areas for further research.
Measured: Prior to treatment and at 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2012 (estimated)
- Study startOct 2012
- Primary completionAug 2014
- Study completionAug 2014
Why it stopped: Lack of accrual and funding expires in June, 2014.
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.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Daniel A. Hamstra, M.D., Ph.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01642732
- Sponsor's protocol ID
- UMCC 2011.008
- Other IDs
- HUM00047650
- Status last verified
- May 2017
- First submitted
- 24 Mar 2012
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-institutional Phase I and Biomarker Study of Everolimus Added to Combined Hormonal and Radiation Therapy for High Risk Prostate Cancer
- ClinicalTrials.gov ID
- NCT01642732
- Acronym / sponsor ID
- UMCC 2011.008
- Conditions
- Prostate Cancer
- Keywords
- Prostate, Cancer, Everolimus, Radiation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual and funding expires in June, 2014.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Oct 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 17 Jul 2012 (estimated)
- Results
- Posted 20 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study are to:
- Determine the safest and highest dose of the study drug RAD001 (Everolimus) that can be taken in combination with hormonal and radiation therapy in men with high risk prostate cancer.
- Evaluate changes in patient reported quality of life
- Evaluate biomarkers from prostate tumor samples. Biomarkers are various traits which can be used to identify the progress of a disease or condition, which can help researchers determine the effect the study treatment has on the tumor. Biomarkers can also help determine areas for further research.
Detailed description
Prostate cancer is very prevalent with an estimated > 200,000 new cases and > 25,000 deaths attributable to prostate cancer in the United States in 2010. Radiation treatment represents a commonly utilized method to treat prostate cancer with an excellent chance of controlling disease with biochemical control at 5-years in excess of 75% in men with locally confined but intermediate to high-risk disease. However, despite impressive biochemical control, local control remains a problem.
Everolimus is being investigated as an anticancer agent based on its potential to act:
- Directly on the tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity.
Given the prevalence of PTEN deletion in high-risk prostate cancers as well as the evidence that tumor hypoxia leads to increased risks of failure after treatment with hormonal therapy and radiation, we hypothesis that inhibition of mTOR signaling in both tumor and vascular cells using everolimus concurrent with hormonal and radiation therapy will enhance the efficacy of radiation therapy without an unacceptable risk of toxicity in men with high-risk prostate cancer.
Everolimus has not been approved by the FDA for the treatment of prostate cancer by itself or in combination with radiation and hormonal therapy. It is not known if this combination is safe and effective in prostate cancer. The FDA has allowed their combined use in this clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus with combined hormonal and radiation therapy | Experimental | Other: Everolimus, lupron, bicalutamide, and radiationEverolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1. Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks). Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy. Lupron injections will begin on study day 10 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections. Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years
- Participants must be able to care for themselves
- Adequate function
- Adequate kidney function
- Histologically confirmed diagnosis of adenocarcinoma of the prostate with biopsy within 90 days of enrollment
Key exclusion criteria (31 listed)
- Participants currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, targeted therapy, etc.)
- Prior pharmacologic androgen ablation for prostate cancer is not allowed including LHRH agonist therapy or oral anti-androgen therapy.
- o Previous use of either finasteride or dutasteride is allowed
- Participants, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or participants that may require major surgery during the course of the study
- Any previous therapeutic radiation therapy to the pelvis.
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 |
|---|---|---|
| Everolimus, lupron, bicalutamide, and radiationAlso: afinitor, RAD-001, Casodex, LeuprolideEverolimus - there are five dose levels (2.5mg. every 48 hrs.,2.5mg./day, 5mg./day, 7.5mg./day, and 10mg./day) based on the initial expectations of toxicity and the incidence of toxicity of subjects already treated. Subjects will be on one dose level throughout the study. Subjects will receive everolimus starting on study day 1. Radiation therapy will start on day 60-70 (44 treatments, at 5 treatments a week for a little longer than 8 weeks). Bicalutamide (50 mg. tablets daily) will begin on study day 10-14, approximately 2 months prior to Radiation Therapy. Lupron injections will begin on study day 15 to 25, approximately 2 months prior to Radiation Therapy. The typical dose schedule is either one injection (22.5 mg. dose)every 3 months for a total of 8 injections or one injection (30 mg. dose) every 4 months for a total of 6 injections. Radiation, bicalutamide, and everolimus will end between study day 120-130. Lupron will end at 24 months on study. | Other | Everolimus with combined hormonal and radiation therapy |
Primary outcome
Number of Patients With Adverse Events on Oral Everolimus in Combination With Hormonal Ablation and External Beam Radiation
Time frame: 64 months after beginning everolimus
1 secondary outcome
Difference in Serologic Everolimus and Prostate Biomarker Levels Before and After Treatment With Everolimus
Time frame: Prior to treatment and at 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Daniel A. Hamstra, M.D., Ph.D. principal investigator
University of Michigan Rogel Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Everolimus, lupron, bicalutamide, and radiation in people with Prostate Cancer, run by University of Michigan Rogel Cancer Center at 2 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?
The sponsor lists 9 inclusion and 31 exclusion criteria. 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: stopped early, as of the sponsor's last update on 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 20 Nov 2014). 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 Adverse Events on Oral Everolimus in Combination With Hormonal Ablation and External Beam Radiation (time frame: 64 months after beginning everolimus). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 May 2017.