Metastatic Prostate CancerPhase 1NCT02500901
Enzalutamide and Niraparib in the Treatment of Metastatic Castrate-Resistant Prostate Cancer (CRPC)
A Phase 1 study testing Enzalutamide and Niraparib in people with Metastatic Prostate Cancer, run by Paul Mathew, MD at 1 site in United States.
Trial summary
This is a phase I study to determine the safety and feasibility of the combination of enzalutamide and niraparib in subjects with metastatic castration-resistant prostate cancer (CRPC). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- Enzalutamide and Niraparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to 10 May 2016
- 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
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 14 days prior to registration.
- Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 120 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
- Documented histologically or cytologically confirmed adenocarcinoma of the prostate.
- Ongoing androgen deprivation therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or bilateral orchiectomy. Subjects who have not undergone orchiectomy must plan to continue GnRH analogue therapy for the duration of the trial.
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- All subjects on oral anti-androgen therapy must have been off therapy for at least 4 weeks prior to registration (6 weeks for bicalutamide) to exclude an anti-androgen withdrawal response. Patients who received secondary anti-androgen therapy and did not exhibit a >50% PSA decline, or subjects with any rise in PSA, objective or symptomatic progression following anti-androgen withdrawal will not be required to meet this withdrawal requirement.
- Documented metastatic disease with prostate-specific antigen (PSA) progression, radiographic progression, or both, despite receiving luteinizing hormone releasing hormone (LHRH) analogue therapy or orchiectomy with a serum testosterone level of 50 ng/dL or less.
- PSA progression is defined as three successive rising PSA values with an interval of at least one week between determinations.
- Radiographic progression is defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or at least two new lesions on bone scan.
- At screening the serum testosterone must be 50 ng/dL or less and the PSA must be greater or equal to 2 ng/mL.
- Estimated life expectancy > 6 months
- Prior treatment of CRPC, including docetaxel, cabazitaxel, sipuleucel-T, or Radium-223 is allowed.
- Prior therapy with abiraterone allowed for a maximum of 9 subjects.
- Prior chemotherapy must be completed at least 28 days prior to registration and the participant subject must have recovered from the acute toxic effects.
Who cannot join
- Prior enzalutamide or other next-generation androgen receptor- (AR) targeting therapy.
- Prior PARP-inhibitor therapy.
- History of or active central nervous system (CNS) metastases. Subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis.
- Radioisotope or external beam radiation exposure in the last 4 weeks. Exposure to strontium, regardless of when exposure occurred.
- Prior radiation to 25% or more of the bone marrow.
- Treatment with any investigational agent within 28 days prior to registration.
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- Known significant immunodeficiency as determined by the site investigator.
- Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, or other cancer for which the subject has been disease-free or stable for at least one year.
- Prolonged QTc over 470 ms.
- History of seizure.
- Clinically significant active infections on systemic therapy as judged by the site investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Combined Targeting of the Androgen Receptor in Metastatic Castrate-Resistant Prostate Cancer With Enzalutamide and the Poly (ADP- Ribose) Polymerase (PARP) Inhibitor Niraparib: Hoosier Cancer Research Network GU14-202
This is a phase I study to determine the safety and feasibility of the combination of enzalutamide and niraparib in subjects with metastatic castration-resistant prostate cancer (CRPC).
Read the detailed description
OUTLINE: This is a multi-center trial.
INVESTIGATIONAL TREATMENT:
Each eligible subject will begin treatment with a 28-day enzalutamide 160 mg/day lead-in cycle. If a subject is able to tolerate the lead-in enzalutamide cycle without Grade 2 or Grade 2-4 drug-related toxicity, dose reduction, or missed doses due to toxicity, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg daily.
Niraparib will be dosed daily starting at 100mg (dose level 1). Six subjects will be enrolled per dose level. If less than 33% of the subjects experience a dose-limiting toxicity (DLT) at the beginning of cycle 2, then the daily dose of niraparib will escalate to 200mg (dose level 2). If dose level 2 is similarly tolerated, then the daily dose of niraparib escalate to 300mg (dose level 3).
The following required laboratory values must be obtained within 14 days prior to registration for protocol therapy:
Hematopoietic:
- White blood cell count (WBC) ≥ 1500/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 150,000/µL
- Absolute neutrophil count (ANC) ≥ 1500/mm3
Renal:
- Calculated creatinine clearance of ≥ 40 cc/min using the Cockcroft-Gault formula
Hepatic:
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 × ULN
- Conditions
- Metastatic Prostate Cancer
- Being tested
- Enzalutamide, Niraparib
- Keywords
- Enzalutamide, Niraparib, PARP-1 inhibitor, PARP-2 inhibitor, Castrate-Resistant 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.
EnzalutamideDrug
Also called Xtandi
Following completion of 28-day lead-in cycle, enzalutamide 160 mg PO daily will continue to be administered in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.
NiraparibDrug
Niraparib will be administered daily in three dose-escalation cohorts of 6 subjects per dose levels of 100mg PO, 200mg PO or 300mg PO in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Treatment | Experimental | Subjects will receive enzalutamide 160 mg/day PO in a 28-day lead-in cycle to assess tolerability. If well-tolerated, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg PO daily. Niraparib will be administered in three dose-escalation cohorts of 100mg PO, 200mg PO or 300 mg PO daily. Six subjects will be enrolled at each dose level. Each cycle will be 28 days. Combination treatment will continue until documented progression, unmanageable toxicity, or subject or treating investigator decision to discontinue for any reason. Receives: Drug: Enzalutamide; Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) for Subjects Receiving Enzalutamide With Niraparib Without Experiencing Dose-limiting Toxicity(s) (DLT)
MTD of niraparib in combination with enzalutamide and MTD for phase II testing.
Measured: From the start of combination treatment D29 until 30 days after last dose of study treatment per CTCAE v4, assessed up to 52 weeks
Secondary outcomes (2)
Progression-free Survival (PFS) With Enzalutamide and Niraparib Combination Therapy.
PFS per RECIST v1.1 for subjects on this combination therapy.
Measured: From the date of enrollment until the criteria for disease progression is met as defined by RECIST 1.1 or death from any cause, whichever occurs first, assessed up to 52 weeks
Objective Response (OR) Rates for All Subjects With Confirmed Partial Response (PR) or Complete Response (CR) Outcomes, Per RECIST v1.1
OR outcomes for subjects on this combination therapy, per RECIST v1.1
Measured: From the date of enrollment until the date of documented disease progression or the date of death from any cause, whichever occurs first, assessed up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study startMar 2016
- Primary completion10 May 2016
- Study completion10 May 2016
Why it stopped: Suspended by funder
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 Metastatic Prostate CancerStudies of the same condition, open and under way.
- 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paul Mathew, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Tesaro, Inc.
- Responsible party
- Sponsor-investigator, Paul Mathew, MD, Hoosier Cancer Research Network
- Investigators
- Paul Mathew, M.D., Study chair, Hoosier Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500901
- Sponsor's protocol ID
- HCRN GU14-202
- Status last verified
- Oct 2019
- First submitted
- 2 Jul 2015
- Last updated
- 21 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Targeting of the Androgen Receptor in Metastatic Castrate-Resistant Prostate Cancer With Enzalutamide and the Poly (ADP- Ribose) Polymerase (PARP) Inhibitor Niraparib: Hoosier Cancer Research Network GU14-202
- ClinicalTrials.gov ID
- NCT02500901
- Acronym / sponsor ID
- HCRN GU14-202
- Conditions
- Metastatic Prostate Cancer
- Keywords
- Enzalutamide, Niraparib, PARP-1 inhibitor, PARP-2 inhibitor, Castrate-Resistant Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Suspended by funder
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Paul Mathew, MDUniversity, hospital or other
- Collaborators
- Hoosier Cancer Research Network, Tesaro, Inc.
- Study start
- Mar 2016
- Primary completion
- 10 May 2016 (actual)
- Study completion
- 10 May 2016 (actual)
- First posted
- 17 Jul 2015 (estimated)
- Results
- Posted 21 Oct 2019
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 I study to determine the safety and feasibility of the combination of enzalutamide and niraparib in subjects with metastatic castration-resistant prostate cancer (CRPC).
Detailed description
OUTLINE: This is a multi-center trial.
INVESTIGATIONAL TREATMENT:
Each eligible subject will begin treatment with a 28-day enzalutamide 160 mg/day lead-in cycle. If a subject is able to tolerate the lead-in enzalutamide cycle without Grade 2 or Grade 2-4 drug-related toxicity, dose reduction, or missed doses due to toxicity, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg daily.
Niraparib will be dosed daily starting at 100mg (dose level 1). Six subjects will be enrolled per dose level. If less than 33% of the subjects experience a dose-limiting toxicity (DLT) at the beginning of cycle 2, then the daily dose of niraparib will escalate to 200mg (dose level 2). If dose level 2 is similarly tolerated, then the daily dose of niraparib escalate to 300mg (dose level 3).
The following required laboratory values must be obtained within 14 days prior to registration for protocol therapy:
Hematopoietic:
- White blood cell count (WBC) ≥ 1500/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelets ≥ 150,000/µL
- Absolute neutrophil count (ANC) ≥ 1500/mm3
Renal:
- Calculated creatinine clearance of ≥ 40 cc/min using the Cockcroft-Gault formula
Hepatic:
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 × ULN
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Treatment | Experimental | Drug: Enzalutamide, Drug: NiraparibSubjects will receive enzalutamide 160 mg/day PO in a 28-day lead-in cycle to assess tolerability. If well-tolerated, cycle 1 of combined enzalutamide and niraparib will commence. Enzalutamide will continue at 160 mg PO daily. Niraparib will be administered in three dose-escalation cohorts of 100mg PO, 200mg PO or 300 mg PO daily. Six subjects will be enrolled at each dose level. Each cycle will be 28 days. Combination treatment will continue until documented progression, unmanageable toxicity, or subject or treating investigator decision to discontinue for any reason. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 14 days prior to registration.
- Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 120 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
- Documented histologically or cytologically confirmed adenocarcinoma of the prostate.
Key exclusion criteria (11 listed)
- Prior enzalutamide or other next-generation androgen receptor- (AR) targeting therapy.
- Prior PARP-inhibitor therapy.
- History of or active central nervous system (CNS) metastases. Subjects with neurological symptoms must undergo a head computed tomography (CT) scan or brain magnetic resonance imaging (MRI) to exclude brain metastasis.
- Radioisotope or external beam radiation exposure in the last 4 weeks. Exposure to strontium, regardless of when exposure occurred.
- Prior radiation to 25% or more of the bone marrow.
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 |
|---|---|---|
| EnzalutamideAlso: XtandiFollowing completion of 28-day lead-in cycle, enzalutamide 160 mg PO daily will continue to be administered in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason. | Drug | Experimental Treatment |
| NiraparibNiraparib will be administered daily in three dose-escalation cohorts of 6 subjects per dose levels of 100mg PO, 200mg PO or 300mg PO in 28-day cycles until documented progression, unmanageable toxicity, or decision to discontinue for any reason. | Drug | Experimental Treatment |
Primary outcome
Maximum Tolerated Dose (MTD) for Subjects Receiving Enzalutamide With Niraparib Without Experiencing Dose-limiting Toxicity(s) (DLT)
Time frame: From the start of combination treatment D29 until 30 days after last dose of study treatment per CTCAE v4, assessed up to 52 weeks
MTD of niraparib in combination with enzalutamide and MTD for phase II testing.
2 secondary outcomes
Progression-free Survival (PFS) With Enzalutamide and Niraparib Combination Therapy.
Time frame: From the date of enrollment until the criteria for disease progression is met as defined by RECIST 1.1 or death from any cause, whichever occurs first, assessed up to 52 weeks
Objective Response (OR) Rates for All Subjects With Confirmed Partial Response (PR) or Complete Response (CR) Outcomes, Per RECIST v1.1
Time frame: From the date of enrollment until the date of documented disease progression or the date of death from any cause, whichever occurs first, assessed up to 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Hoosier Cancer Research Network WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Paul Mathew, M.D. study chair
Hoosier Cancer Research Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Enzalutamide and Niraparib in people with Metastatic Prostate Cancer, run by Paul Mathew, MD 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 15 inclusion and 11 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 21 Oct 2019. 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 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 21 Oct 2019). 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?
Maximum Tolerated Dose (MTD) for Subjects Receiving Enzalutamide With Niraparib Without Experiencing Dose-limiting Toxicity(s) (DLT) (time frame: From the start of combination treatment D29 until 30 days after last dose of study treatment per CTCAE v4, assessed up to 52 weeks). 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 21 Oct 2019.