ATM Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Homologous Recombination Deficiency, Prostate Carcinoma Metastatic in the Bone, PSA Level Greater Than or Equal to Two, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7
Conditions
Brief summary
This phase II trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer (spread outside of prostate and resistant to testosterone suppression) with homologous recombination DNA repair deficiency. Chemotherapy drugs, such as docetaxel and carboplatin, work to stop the growth of cancer cells, by stopping them from dividing or spreading. Rucaparib camsylate may stop the growth of tumor cells with defects in the ability to repair mistakes in DNA by forcing additional errors so that the cancer cells cannot overcome the number of errors and will then die. Giving induction docetaxel and carboplatin followed by maintenance rucaparib camsylate may work better in treating patients with castration resistant prostate cancer.
Detailed description
OUTLINE: INDUCTION: Patients receive docetaxel intravenously (IV) and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive rucaparib camsylate orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGCarboplatin
Given IV
DRUGDocetaxel
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Given PO
DRUGRucaparib
Given PO
Sponsors
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information * Histologically or cytologically confirmed adenocarcinoma of the prostate (excluding predominant small cell histology) * Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy * Castration resistant prostate cancer as defined by serum testosterone \< 50 ng/ml and PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart * Presence of metastatic disease on bone or computed tomography (CT) scan * Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) * Bone disease on bone scan * Prior therapy with sipuleucel-T, abiraterone, enzalutamide, docetaxel, and/or cabazitaxel; there is no limit to the number of prior treatment regimens in the castration resistant setting, so long as prior therapy does not include platinum chemotherapy or a PARP inhibitor; prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as it has been at least 6 months since last dose * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1 * Life expectancy \>= 12 weeks * No prior malignancy is allowed except: * Adequately treated basal cell or squamous cell skin cancer or * In situ carcinoma of any site or * Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed) * Documented evidence of at least ONE or MORE of the following: \* Pathogenic mutation or inactivating alteration of a gene involved in homologous recombination repair in the tumor * Note, that if this alteration is identified in a circulating tumor deoxyribonucleic acid (ctDNA) assay, the variant-allele fraction must be \> 20% to indicate relevance to predominant tumor clone * Mutation in one or more other genes involved in homologous DNA recombination repair in the tumor may be included at investigator's discretion * Homologous recombination repair deficiency by genomic signature in the tumor by BROCA-HR, Foundation One or equivalent assay * Presence of pathogenic or likely pathogenic germline mutation/variant in BRCA2, BRCA1, ATM or PALB2 * Note: Germline mutations in other HR genes will be considered at investigator's discretion) * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 14 days of first dose of study drug) * Platelets \> 100 x 10\^9/L (within 14 days of first dose of study drug) * Hemoglobin \>= 9 g/dL (within 14 days of first dose of study drug) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN; if liver metastases, then =\< 5 x ULN (within 14 days of first dose of study drug) * Bilirubin =\< 1.5 x ULN (\< 2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome) (within 14 days of first dose of study drug) * Serum creatinine =\< 1.5 x ULN or estimated glomerular filtration rate (GFR) \>= 45 mL/min using the Cockcroft Gault formula (within 14 days of first dose of study drug)
Exclusion criteria
* Currently receiving active therapy for other neoplastic disorders * Symptomatic and/or untreated central nervous system (CNS) metastases; patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, active or symptomatic viral hepatitis or chronic liver disease * Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of \< 35 % at baseline * Treatment with an investigational therapeutic drug within 30 days of cycle 1 * Prior therapy with a PARP inhibitor (e.g., olaparib, talazoparib, veliparib, niraparib, rucaparib) * Prior therapy with a platinum chemotherapy (e.g. cisplatin, carboplatin, oxaliplatin) in the castration resistant setting; (prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as time since last dose is 6 months or greater) * Active, ongoing toxicity (Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2 or higher) from prior therapy * Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding and/or giving of informed consent * Pre-existing duodenal stent and/ or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib * Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression Free Survival Assessed by Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1/Prostate Cancer Working Group 3 (PCWG3) Criteria | From first dose of docetaxel/carboplatin to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, assessed up to 3.75 years. | Radiologic progression free survival (rPFS) is defined as the time from first dose of docetaxel/carboplatin to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by investigator assessment using the RECIST 1.1/PCWG3 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) of Measurable Disease (PCWG3) (Complete Response or Partial Response) Assessed by Modified RECIST Version 1.1 Criteria | Up to 3.75 years | Overall response rate of measurable disease (PCWG3): radiologic ORR (CR or PR per modified RECIST Version 1.1 criteria and no bone progression per PCWG3 prior to a CR or PR) by investigator assessment in patients with measurable visceral and/or nodal disease at baseline per IRR (Cohort A). An analysis of radiologic ORR by the investigator will also be conducted as supportive to the primary endpoint. |
| Prostate-specific Antigen (PSA) Nadir After Induction | Up to 13 weeks | Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90). Number of patients achieving a PSA decline from baseline of ≥50% (PSA50) or ≥90% (PSA90). The change in PSA was calculated relative to the PSA level at the start of cycle 1. |
| PSA Nadir After Maintenance | Up to 3.5 years | Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90) using postchemotherapy PSA as the baseline. The most recent PSA level before PARPi initiation was used as the baseline PSA. Number of patients achieving a PSA decline from baseline of ≥50% (PSA50) or ≥90% (PSA90). |
| PSA Response Duration | From the date that a response (PSA decrease >= 50%) is first reported to the time that PSA progression is first documented, assessed up to 3.75 years | PSA-response duration: duration of confirmed response is defined as the time from the date that a response (PSA decrease ≥ 50%) is first reported to the time that PSA progression is first documented. |
| Time to PSA Progression (PCWG3) | From first dose of docetaxel/carboplatin to the date that a >= 25% increase and absolute increase of >= 2 ng/mL above the nadir (or baseline value for patients who did not have a decline in PSA) in PSA was measured, assessed up to 3.75 years. | Time to PSA progression is defined as the time from first dose of docetaxel/carboplatin to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for patients who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHeather H. Cheng
Fred Hutch/University of Washington Cancer Consortium
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| BRCA/ATM/other HR gene mutation status ATM | 7 participants |
| BRCA/ATM/other HR gene mutation status BRCA1 | 3 participants |
| BRCA/ATM/other HR gene mutation status BRCA2 | 8 participants |
| BRCA/ATM/other HR gene mutation status CHD1 + SPOP | 1 participants |
| BRCA/ATM/other HR gene mutation status FANCA | 1 participants |
| BRCA/ATM/other HR gene mutation status PALB2 | 1 participants |
| Clinical Stage at Diagnosis De novo metastatic disease | 12 Participants |
| Clinical Stage at Diagnosis Localized disease at diagnosis | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Primary treatment (radical prostatectomy or radiation) Neither | 12 Participants |
| Primary treatment (radical prostatectomy or radiation) Prostatectomy | 5 Participants |
| Primary treatment (radical prostatectomy or radiation) Radiation | 1 Participants |
| Prior therapies for castration resistant prostate cancer 1 Therapy | 4 Participants |
| Prior therapies for castration resistant prostate cancer 2 Therapies | 8 Participants |
| Prior therapies for castration resistant prostate cancer 3 or more Therapies | 6 Participants |
| PSA at Diagnosis Participant 1 | 16 ng/mL |
| PSA at Diagnosis Participant 10 | 7 ng/mL |
| PSA at Diagnosis Participant 11 | 25 ng/mL |
| PSA at Diagnosis Participant 12 | 36 ng/mL |
| PSA at Diagnosis Participant 13 | 17 ng/mL |
| PSA at Diagnosis Participant 14 | 13 ng/mL |
| PSA at Diagnosis Participant 15 | 2040 ng/mL |
| PSA at Diagnosis Participant 16 | 35 ng/mL |
| PSA at Diagnosis Participant 17 | 4374 ng/mL |
| PSA at Diagnosis Participant 18 | 1101 ng/mL |
| PSA at Diagnosis Participant 2 | 5 ng/mL |
| PSA at Diagnosis Participant 3 | 42 ng/mL |
| PSA at Diagnosis Participant 4 | 129 ng/mL |
| PSA at Diagnosis Participant 5 | 156 ng/mL |
| PSA at Diagnosis Participant 6 | 540 ng/mL |
| PSA at Diagnosis Participant 7 | 6 ng/mL |
| PSA at Diagnosis Participant 8 | 588 ng/mL |
| PSA at Diagnosis Participant 9 | 132 ng/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 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 | 1 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
| TNM Stage at Diagnosis pT3aN0 | 1 Participants |
| TNM Stage at Diagnosis pT3aR0N1 | 1 Participants |
| TNM Stage at Diagnosis pT3bpN1 | 1 Participants |
| TNM Stage at Diagnosis T2aN1M0 | 1 Participants |
| TNM Stage at Diagnosis T3bN0 | 1 Participants |
| TNM Stage at Diagnosis Unknown | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 1 / 16 |
| other Total, other adverse events | 18 / 18 | 16 / 16 |
| serious Total, serious adverse events | 2 / 18 | 1 / 16 |
Outcome results
None listed