Prostate CancerPhase 1/2NCT03572478
Rucaparib and Nivolumab in Patients With Prostate or Endometrial Cancer
A Phase 1/2 study testing Rucaparib and Nivolumab in people with Prostate Cancer and Endometrial Cancer, run by University of Chicago at 1 site in United States.
Trial summary
This is a phase 1/phase 2a study of the combination of immune checkpoint inhibitor (nivolumab) in combination with the PARP inhibitor (rucaparib) for patients with metastatic castration resistant prostate cancer (mCRPC) and metastatic/recurrent endometrial cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostate Cancer, Endometrial Cancer
- What is being tested?
- Rucaparib and Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Aug 2018to 1 Oct 2020
- Phase
- Phase 1/2
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have the ability to understand and the willingness to signed a written informed consent document.
- Patients must have histologically or cytologically confirmed CRPC or endometrial cancer that is metastatic. Evidence of disease progression on a prior therapy is not required.
- Patients must have at least one lesion that is amenable to biopsy and the treating physician must deem this safe.
- Patient must be willing to undergo two mandatory research-only biopsies.
- Prostate cancer patients:
- Patients must be surgically or medically castrated, with serum testosterone levels ≤ 50 ng/mL Patients being treated with Gonadotropin-releasing hormone (GnRH) agonists must have such therapy continued throughout the study.
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- Patients should have received at least one androgen receptor (AR)-targeted therapy with abiraterone acetate or enzalutamide. Multiple lines of prior AR-targeted therapy and chemotherapy are permitted. A washout of two weeks from prior endocrine therapy (other than GnRH agonist); four weeks washout period from prior cytotoxic chemotherapy or other anticancer agents is required (prior to day 1 of study therapy); six weeks washout period to allow for anti-androgen withdrawal for patients managed with antiandrogen therapy such as bicalutamide.
- Endometrial cancer patients:
- An unlimited number of prior hormonal and/or chemotherapy regimens are permitted. A washout of two weeks from prior endocrine therapy (other than GnRH agonist) and four weeks from prior cytotoxic chemotherapy or other anticancer agents is required (prior to day 1 of study therapy).
- At least 5 days should have elapsed since any non-study related minor surgical procedure and at least 21 days since any major surgical procedure prior to the first dose of rucaparib and the first dose of nivolumab.
- Must have an ability to swallow pills or capsules. Patients should have no current clinical evidence of bowel obstruction.
- Age must be ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status must be ≤ 1
- Patients must have normal hepatic, renal and marrow function as defined below:
- hemoglobin > 10 g/dL
- leukocytes ≥ 3,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 150,000/mcL
- total bilirubin within normal institutional limits
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × institutional upper limit of normal
- creatinine within normal institutional limits OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose of study drug. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of first dose of study drug are strongly encouraged to receive palliative radiotherapy prior to enrollment.
- Reproductive Status: Rucaparib caused post-implantation loss (100% early resorptions) at all doses administered in an embryo-fetal development study. Based on its mechanism of action, nivolumab can cause fetal harm when administered to a pregnant woman. Pregnant women are therefore not eligible for this study.
- Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test result less than 3 days prior to administration of the first dose of rucaparib.
- WOCBP must not be considering getting pregnant during the study.
- WOCBP and their male partners must agree to use a highly effective, reliable form of contraception during treatment; for 6 months following the last dose of rucaparib; and for at least 5 months following the last dose of nivolumab.
- Men who are sexually active with WOCBP must agree to use a highly effective, reliable form of contraception during treatment; 6 months following the last dose of rucaparib; and for a period of 7 months after the last dose of nivolumab .
- In addition to the above methods of contraception, use of a condom by male patients is recommended to prevent transfer of drug through semen.
Who cannot join
- Patients with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes, mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, childhood asthma that is not currently active, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted.
- Patients who are receiving any other investigational agents.
- Prior exposure to PD-1 or PD-L1 inhibitors, other immune checkpoint inhibitors (e.g. anti-LAG-3, and anti-CTLA-4 antibodies), or PARP inhibitors.
- Patients with a "currently active" second invasive malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and have been free of disease for ≥ 1 years.
- Patients with known and untreated or progressing brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients whose brain metastases have been treated with surgery and/or radiotherapy and are without evidence of progression on scan for at least 4 weeks, and are off steroids or antiseizure medications, will be eligible .
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- Patients with symptomatic or impending spinal cord compression are not eligible unless appropriately treated.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab or rucaparib.
- Based on in vitro CYP interaction studies, caution should be used for concomitant medications with a narrow therapeutic window that are substrates of CYP2C19, CYP2C9, and/or CYP3A. Selection of an alternate concomitant medication is recommended. Caution should also be exercised for concomitant use of certain statin drugs (e.g. rosuvastatin and fluvastatin) due to potential increase in exposure from inhibition of BCRP and CYP2C9. An updated list of clinically relevant P450 drug interactions (e.g: Flockhart Table http://medicine.iupui.edu/clinpharm/ddis/main-table/) should be reviewed while screening patients for study.
- Patients taking warfarin should have international normalized ration (INR) monitored regularly according to standard institutional practices
- Because rucaparib is a moderate inhibitor of P-gp in vitro, caution should be exercised for patients receiving rucaparib and requiring concomitant medication with digoxin. Patients taking digoxin should have their digoxin levels monitored after starting rucaparib and then regularly per standard clinical practice.
- Patients on parenteral nutrition are not eligible. Patients must not have a pre-existing duodenal stent or any gastrointestinal disorder or defect that would, in the opinion of the treating investigator, interfere with absorption of rucaparib.
- Uncontrolled intercurrent illness including, but not limited to, requirement for oxygen therapy, ongoing or active infection other than minor urinary tract infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known history of chronic hepatitis B or C as evidenced by:
- Positive test for hepatitis B surface antigen
- Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR])
- Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by polymerase chain reaction (PCR) are eligible.
- Human Immunodeficiency Virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with rucaparib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Prior organ allograft or allogeneic bone marrow transplantation.
- Adverse effect of prior therapy not improved to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or below with the exception of alopecia or lymphopenia. Ongoing Grade 2 non-hematologic toxicity (e.g. neuropathy) related to most recent treatment regimen may be permitted with prior advanced approval from the Lead Principal Investigator.
- Initiated denosumab or bisphosphonate therapy or adjusted denosumab or bisphosphonate dose/regimen within 4 weeks prior to first dose of rucaparib. Patients on a stable denosumab or bisphosphonate regimen are eligible and may continue treatment.
- Evidence or history of active or latent tuberculosis infection including purified protein derivative (PPD) recently converted to positive.
- Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study drug. The use of inactivated seasonal influenza vaccines, e.g., Fluzone®, will be permitted on study without restriction.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Medical Center
Chicago, Illinois, 60637
About this study
Official title: A Phase Ib/IIa Study of Rucaparib (PARP Inhibitor) Combined With Nivolumab in Metastatic Castrate - Resistant Prostate Cancer and Advanced/Recurrent Endometrial Cancer
This is a phase 1/phase 2a study of the combination of immune checkpoint inhibitor (nivolumab) in combination with the PARP inhibitor (rucaparib) for patients with metastatic castration resistant prostate cancer (mCRPC) and metastatic/recurrent endometrial cancer.
In the phase 1 portion, the safety of the combination dosing will be determined. If the combination dosing is determined to be safe and feasible, the study will move onto phase 2a.
In the phase 2a portion, participants will be randomized to receive either: rucaparib alone, nivolumab alone, or combination therapy (rucaparib and nivolumab).
- Conditions
- Prostate Cancer, Endometrial Cancer
- Being tested
- Rucaparib, Nivolumab
- Medical subject headings
- Prostatic Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Also called Rubraca(R)
600 mg taken by mouth twice daily.
NivolumabDrug
Also called Opdivo(R)
480 mg given by intravenous (IV) infusion every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy (Phase 1b Cohort) | Experimental | Participants will receive rucaparib plus nivolumab in 4 week cycles. Receives: Drug: Rucaparib; Drug: Nivolumab |
| Rucaparib (Phase 2b Randomized Cohort) | Experimental | Participants randomized to receive rucaparib alone in 4 week cycles. Receives: Drug: Rucaparib |
| Nivolumab (Phase 2b Randomized Cohort) | Experimental | Participants randomized to receive nivolumab alone in 4 week cycles. Receives: Drug: Nivolumab |
| Combination Therapy (Phase 2b Randomized Cohort) | Experimental | Participants randomized to receive rucaparib plus nivolumab in 4 week cycles. Participants will receive rucaparib alone in cycle 1 and begin nivolumab on day 1 of Cycle 2. Receives: Drug: Rucaparib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose Limiting Toxicities (DLT) (Phase 1)
Dose limiting toxicities (DLT) is measured by patients with grade 3 or 4 toxicity within 4 weeks of starting leading to discontinuation of rucaparib for at least 1 week
Measured: 8 weeks
Frequency of Patients With T Cell Inflammation in the Tumor Compared Between Treatment Arms (Phase 2)
Measured: 4 weeks
Secondary outcomes (6)
Time to Disease Progression in Prostate Cancer Patients (Phase 2)
Measured: 24 months
Time to Disease Progression in Endometrial Cancer Patients (Phase 2)
Measured: 24 months
Response Rate in Prostate Cancer Patients (Phase 2)
Measured: 24 months
Response Rate in Endometrial Cancer Patients (Phase 2)
Measured: 24 months
Changes in Number of T Cells in Tumor Samples Compared Between Treatment Arms (Phase 2)
Measured: 4 weeks
Correlation of Change in T Cells in Tumor Samples and PTEN Mutation Status (Phase 2)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start14 Aug 2018
- Primary completion29 Feb 2020
- Study completion1 Oct 2020
Why it stopped: The study was terminated due to lack of efficacy.
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 ChicagoThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Clovis Oncology, Inc.
- Responsible party
- Sponsor
- Investigators
- Walter Stadler, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572478
- Sponsor's protocol ID
- IRB18-0154
- Status last verified
- Feb 2021
- First submitted
- 19 Jun 2018
- Last updated
- 9 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/IIa Study of Rucaparib (PARP Inhibitor) Combined With Nivolumab in Metastatic Castrate - Resistant Prostate Cancer and Advanced/Recurrent Endometrial Cancer
- ClinicalTrials.gov ID
- NCT03572478
- Acronym / sponsor ID
- IRB18-0154
- Conditions
- Prostate Cancer, Endometrial Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to lack of efficacy.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Clovis Oncology, Inc.
- Study start
- 14 Aug 2018 (actual)
- Primary completion
- 29 Feb 2020 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 28 Jun 2018 (actual)
- Results
- Posted 12 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1/phase 2a study of the combination of immune checkpoint inhibitor (nivolumab) in combination with the PARP inhibitor (rucaparib) for patients with metastatic castration resistant prostate cancer (mCRPC) and metastatic/recurrent endometrial cancer.
In the phase 1 portion, the safety of the combination dosing will be determined. If the combination dosing is determined to be safe and feasible, the study will move onto phase 2a.
In the phase 2a portion, participants will be randomized to receive either: rucaparib alone, nivolumab alone, or combination therapy (rucaparib and nivolumab).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy (Phase 1b Cohort) | Experimental | Drug: Rucaparib, Drug: NivolumabParticipants will receive rucaparib plus nivolumab in 4 week cycles. |
| Rucaparib (Phase 2b Randomized Cohort) | Experimental | Drug: RucaparibParticipants randomized to receive rucaparib alone in 4 week cycles. |
| Nivolumab (Phase 2b Randomized Cohort) | Experimental | Drug: NivolumabParticipants randomized to receive nivolumab alone in 4 week cycles. |
| Combination Therapy (Phase 2b Randomized Cohort) | Experimental | Drug: Rucaparib, Drug: NivolumabParticipants randomized to receive rucaparib plus nivolumab in 4 week cycles. Participants will receive rucaparib alone in cycle 1 and begin nivolumab on day 1 of Cycle 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Patients must have the ability to understand and the willingness to signed a written informed consent document.
- Patients must have histologically or cytologically confirmed CRPC or endometrial cancer that is metastatic. Evidence of disease progression on a prior therapy is not required.
- Patients must have at least one lesion that is amenable to biopsy and the treating physician must deem this safe.
- Patient must be willing to undergo two mandatory research-only biopsies.
- Prostate cancer patients:
Key exclusion criteria (23 listed)
- Patients with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes, mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, childhood asthma that is not currently active, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted.
- Patients who are receiving any other investigational agents.
- Prior exposure to PD-1 or PD-L1 inhibitors, other immune checkpoint inhibitors (e.g. anti-LAG-3, and anti-CTLA-4 antibodies), or PARP inhibitors.
- Patients with a "currently active" second invasive malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and have been free of disease for ≥ 1 years.
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 |
|---|---|---|
| RucaparibAlso: Rubraca(R)600 mg taken by mouth twice daily. | Drug | Combination Therapy (Phase 1b Cohort), Combination Therapy (Phase 2b Randomized Cohort), Rucaparib (Phase 2b Randomized Cohort) |
| NivolumabAlso: Opdivo(R)480 mg given by intravenous (IV) infusion every 4 weeks. | Drug | Combination Therapy (Phase 1b Cohort), Combination Therapy (Phase 2b Randomized Cohort), Nivolumab (Phase 2b Randomized Cohort) |
Primary outcome
Percentage of Participants With Dose Limiting Toxicities (DLT) (Phase 1)
Time frame: 8 weeks
Dose limiting toxicities (DLT) is measured by patients with grade 3 or 4 toxicity within 4 weeks of starting leading to discontinuation of rucaparib for at least 1 week
Frequency of Patients With T Cell Inflammation in the Tumor Compared Between Treatment Arms (Phase 2)
Time frame: 4 weeks
6 secondary outcomes
Time to Disease Progression in Prostate Cancer Patients (Phase 2)
Time frame: 24 months
Time to Disease Progression in Endometrial Cancer Patients (Phase 2)
Time frame: 24 months
Response Rate in Prostate Cancer Patients (Phase 2)
Time frame: 24 months
Response Rate in Endometrial Cancer Patients (Phase 2)
Time frame: 24 months
Changes in Number of T Cells in Tumor Samples Compared Between Treatment Arms (Phase 2)
Time frame: 4 weeks
Correlation of Change in T Cells in Tumor Samples and PTEN Mutation Status (Phase 2)
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- 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.
Walter Stadler, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rucaparib and Nivolumab in people with Prostate Cancer and Endometrial Cancer, run by University of Chicago at 1 site 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 28 inclusion and 23 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 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
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 12 Feb 2021). 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?
Percentage of Participants With Dose Limiting Toxicities (DLT) (Phase 1) (time frame: 8 weeks). The study lists 2 primary outcomes in all. 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 9 Mar 2021.