Prostate Cancer
Conditions
Brief summary
This is a single arm, open label, phase II trial to assess efficacy of rucaparib.
Interventions
DRUGRucaparib
Treatment with rucaparib will begin on Cycle 1 Day 1 and continue at 600 mg twice daily. Therapy continues until Prostate Specific Antigen (PSA) progression or intolerable toxicities.
Sponsors
Clovis Oncology, Inc.
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single arm, open label, phase II trial to assess efficacy of rucaparib
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hormone-sensitive, histologically proven adenocarcinoma of the prostate with BRCAness (defined as an alteration in one or more of the following genes: BARD1, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, NBN, PALB2, RAD51C, RAD51D, RAD51, RAD51B) from soft-tissue based genomic testing or liquid biopsy based genomic or genetic testing. Pathogenic or likely pathogenic alterations are accepted. * Eastern Cooperative Oncology Group (ECOG)/Zubrod score of 0-2. * At a minimum, subjects must have received definitive local therapy with curative intent (i.e., prostatectomy, and/or radiation therapy) with or without systemic therapy. * Testosterone level is \> 50 ng/dL. * Be at least 18 years old at the time the informed consent form is signed. * Demonstrate adequate organ function as defined in the table in the protocol, all screening labs should be performed within 28 days of treatment initiation. * Highly effective barrier methods must be used with all sexual activity and contraception methods must be practiced for all subjects throughout the study and for at least 6 months after last rucaparib treatment administration if the risk of conception exists (section 7.2). * Recovery to baseline or Grade ≤ 1 CTCAE v5.0 from toxicities related to any prior treatments within the context of their definitive local therapy for their prostate cancer, unless Adverse Event(s) (AE)(s) are clinically nonsignificant and/or stable on supportive therapy. * Subject is able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. * Subject must have confirmed PSA progression based on at least two time points taken at least one week apart to confirm rising trend.
Exclusion criteria
* Subjects with metastases defined by conventional scans (CT, MRI, Nuclear Medicine (NM) Bone Scan). Disease identified on molecular imaging (e.g. fluciclovine-PET) is not exclusionary. * Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 90 days prior to screening. * Pre-existing duodenal stent, recent (within \< 3 months) or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib. * Inability to swallow tablets. * Evidence or history of clinically significant bleeding disorder per the determination of the treating investigator. * Prior systemic therapy within the past 30 days prior to Day 1 (or 5 half-lives of the drug, whichever is shorter). * Diagnosis of another malignancy within 2 years before first dose of study treatment only if the cancer will either interfere with participant safety or interfere with the primary endpoint, per the judgement of the Principal Investigator. Participants, who have been diagnosed with, superficial skin cancers, or localized, low grade tumors deemed cured or with a prolonged natural history (e.g estimated overall survival \> 5 years) may be included. * Prior treatment with any poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, mitoxantrone, cyclophosphamide, or any platinum based chemotherapy. * Clinically significant (i.e., active) cardiovascular disease at the time of enrollment: congestive heart failure (\> New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication. * Other severe acute or chronic medical conditions including cardiovascular, endocrine, neurologic, pulmonary or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. * Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 28 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Specific Antigen Progression Free Survival | From baseline to up to 2 years after study treatment discontinuation; actual max approximately 42 months | The levels of PSA were monitored monthly for comparison to baseline levels until the time of PSA progression, or 2 years after study treatment discontinuation, or study termination, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria. PCWG3 criteria for PSA progression is a rise over baseline of \>= 25% and an absolute rise of \>= 2 ng/mL. Reported as median number of months from baseline to PSA progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) Related to Rucaparib | From first dose of study treatment until 30 days after last dose of study treatment; max 42 months | To assess the safety of rucaparib in participants with biochemically recurrent hormone-sensitive prostate cancer. Severity of adverse events was assessed using CTCAE v5.0 criteria, a 1-5 scale with higher numbers indicating greater severity, where Grade 1 indicates mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated and Grade 5 indicates death related to AE. Each adverse event was also evaluated by the treating investigator to assess its attribution to rucaparib, with options being unrelated, unlikely related, possibly related, probably related, or definitely related to rucaparib. Possibly, probably, and definitely related were grouped together as Related. Reported here are the number of participants with any related AE of the specified grade. Note that there were no Grade 4 or Grade 5 related AEs. |
| Count of Participants With an Undetectable PSA at 6 and 12 Months | At 6 and 12 months after initiation of study therapy | To assess the percentage of participants with an undetectable PSA after initiation of study therapy at 6 and 12 months. Endpoint: the levels of PSA will be monitored monthly for comparison to baseline levels to determine when PSA becomes undetectable. Participants who were not followed for at least 6 months after initiation of study therapy were not able to be evaluated for this time point. |
| Overall Survival (OS) at 2 Years | From start of study treatment until up to 2 years after study treatment discontinuation; actual max approximately 42 months | To evaluate OS in nonmetastatic hormone-sensitive prostrate cancer participants treated with rucaparib. Calculated as the number of participants alive 2 years after study treatment discontinuation or study termination. |
| Count of Participants With 50% or Greater Reduction in PSA Levels | From baseline until up to 2 years after study treatment discontinuation; actual max approximately 42 months | To assess the number of participants with a 50% reduction in PSA levels (PSA50) compared to the baseline value at the time of study enrollment. The levels of PSA will be monitored monthly for comparison to baseline levels. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rucaparib, All Participants Single Arm study, all participants will get rucaparib. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Rucaparib, All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 69 years STANDARD_DEVIATION 5.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Prostate Specific Antigen Progression Free Survival
The levels of PSA were monitored monthly for comparison to baseline levels until the time of PSA progression, or 2 years after study treatment discontinuation, or study termination, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria. PCWG3 criteria for PSA progression is a rise over baseline of \>= 25% and an absolute rise of \>= 2 ng/mL. Reported as median number of months from baseline to PSA progression.
Time frame: From baseline to up to 2 years after study treatment discontinuation; actual max approximately 42 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rucaparib, All Participants | Prostate Specific Antigen Progression Free Survival | 35.37 Months |
Secondary
Count of Participants With 50% or Greater Reduction in PSA Levels
To assess the number of participants with a 50% reduction in PSA levels (PSA50) compared to the baseline value at the time of study enrollment. The levels of PSA will be monitored monthly for comparison to baseline levels.
Time frame: From baseline until up to 2 years after study treatment discontinuation; actual max approximately 42 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rucaparib, All Participants | Count of Participants With 50% or Greater Reduction in PSA Levels | 2 Participants |
Secondary
Count of Participants With an Undetectable PSA at 6 and 12 Months
To assess the percentage of participants with an undetectable PSA after initiation of study therapy at 6 and 12 months. Endpoint: the levels of PSA will be monitored monthly for comparison to baseline levels to determine when PSA becomes undetectable. Participants who were not followed for at least 6 months after initiation of study therapy were not able to be evaluated for this time point.
Time frame: At 6 and 12 months after initiation of study therapy
Population: Three participants did not complete follow-up to 6 months, so only four could be evaluated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rucaparib, All Participants | Count of Participants With an Undetectable PSA at 6 and 12 Months | At 6 months | 1 Participants |
| Rucaparib, All Participants | Count of Participants With an Undetectable PSA at 6 and 12 Months | At 12 months | 1 Participants |
Secondary
Number of Participants With Adverse Events (AEs) Related to Rucaparib
To assess the safety of rucaparib in participants with biochemically recurrent hormone-sensitive prostate cancer. Severity of adverse events was assessed using CTCAE v5.0 criteria, a 1-5 scale with higher numbers indicating greater severity, where Grade 1 indicates mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated and Grade 5 indicates death related to AE. Each adverse event was also evaluated by the treating investigator to assess its attribution to rucaparib, with options being unrelated, unlikely related, possibly related, probably related, or definitely related to rucaparib. Possibly, probably, and definitely related were grouped together as Related. Reported here are the number of participants with any related AE of the specified grade. Note that there were no Grade 4 or Grade 5 related AEs.
Time frame: From first dose of study treatment until 30 days after last dose of study treatment; max 42 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rucaparib, All Participants | Number of Participants With Adverse Events (AEs) Related to Rucaparib | Grade 1 | 7 Participants |
| Rucaparib, All Participants | Number of Participants With Adverse Events (AEs) Related to Rucaparib | Grade 2 | 4 Participants |
| Rucaparib, All Participants | Number of Participants With Adverse Events (AEs) Related to Rucaparib | Grade 3 | 2 Participants |
Secondary
Overall Survival (OS) at 2 Years
To evaluate OS in nonmetastatic hormone-sensitive prostrate cancer participants treated with rucaparib. Calculated as the number of participants alive 2 years after study treatment discontinuation or study termination.
Time frame: From start of study treatment until up to 2 years after study treatment discontinuation; actual max approximately 42 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rucaparib, All Participants | Overall Survival (OS) at 2 Years | 7 Participants |