Description:
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging
chemotherapy using carboplatin, to standard of care chemotherapy for patients who have
metastatic castrate resistant prostate cancer. This trial will use docetaxel or carboplatin
as initial chemotherapy with crossover to the alternate or second-line drug after first
progression for patients with tumors containing BRCA1, BRCA2 or PALB2 inactivating DNA
mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5) first or docetaxel
(75 mg/m2) every 21 days until intolerance, complete response, or progression by Prostate
Cancer Working Group 3 (PCWG3) criteria or 10 cycles (whichever is first).
Participants then crossover from the first-line therapy to the second-line therapy with the
opposite study medication and receive treatment to intolerance or progression or 10 cycles
(whichever is first). Enrolled participants will be allowed to crossover to second line
therapy if they continue to meet initial eligibility criteria, and at least three weeks have
elapsed since last administration of either carboplatin or docetaxel. Throughout the study,
safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of
the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
Title
- Brief Title: BRcA Deficient Prostate Cancer Treated With Carboplatin or Docetaxel
- Official Title: Multicenter Phase II Study of First-line Carboplatin Followed by Docetaxel Versus First-line Docetaxel Followed by Carboplatin for Treatment of Castration Resistant Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
ONCA-009-18F
- SECONDARY ID:
CX-18-006
- SECONDARY ID:
19-08
- SECONDARY ID:
01783
- SECONDARY ID:
01781
- SECONDARY ID:
CX001963-01
- NCT ID:
NCT04038502
Conditions
- Metastatic Castrate Resistant Prostate Cancer
- BRCA1, BRCA2, PALB2 Genetic Mutations
Interventions
| Drug | Synonyms | Arms |
|---|
| Carboplatin | Paraplatin | Treatment Arm 1 - Carboplatin to Docetaxel |
| Docetaxel | Docefrez, Taxotere | Treatment Arm 1 - Carboplatin to Docetaxel |
Purpose
This is an unblinded, randomized clinical study comparing the efficacy of DNA damaging
chemotherapy using carboplatin, to standard of care chemotherapy for patients who have
metastatic castrate resistant prostate cancer. This trial will use docetaxel or carboplatin
as initial chemotherapy with crossover to the alternate or second-line drug after first
progression for patients with tumors containing BRCA1, BRCA2 or PALB2 inactivating DNA
mutations.
Participants are randomized (1:1) and receive either carboplatin (AUC 5) first or docetaxel
(75 mg/m2) every 21 days until intolerance, complete response, or progression by Prostate
Cancer Working Group 3 (PCWG3) criteria or 10 cycles (whichever is first).
Participants then crossover from the first-line therapy to the second-line therapy with the
opposite study medication and receive treatment to intolerance or progression or 10 cycles
(whichever is first). Enrolled participants will be allowed to crossover to second line
therapy if they continue to meet initial eligibility criteria, and at least three weeks have
elapsed since last administration of either carboplatin or docetaxel. Throughout the study,
safety and tolerability will be assessed. Progression will be evaluated with bone scan, CT of
the abdomen/pelvis, or MRI and PSA as per PCWG3 criteria.
Detailed Description
BRACeD Study General Trial Over-view
Research shows that when some changes or mutations occur in the DNA involved with repairing
genes, the risk of cancer increases. Patients who have certain kinds of mutations in their
DNA-repair genes have responded well to drugs which damage DNA but are not part of standard
therapy for prostate cancer, this study is designed to help better understand treatment
options for these patients.
Treatment with a drug called docetaxel is one of the standard chemotherapy treatments for men
with metastatic castration resistant prostate cancer (mCRPC). Carboplatin is a DNA damaging
chemotherapy treatment which is used for treatment of cancer, but is not commonly used for
the treatment of prostate cancer. In early studies, the use of carboplatin has shown very
promising activity in treatment of prostate cancer. This study is being conducted to evaluate
patient response to treatment with docetaxel compared to carboplatin.
Patients wishing to participate in this study are screened for safety and health eligibility
before enrolling.
This study is enrolling 40 male participants total, from across the VAMC nationally who have
the following:
- Metastatic castration-resistant prostate cancer (mCRPC)
- Cancer that has gotten worse, after any number of first-line treatments
- Mutations in DNA-repair genes discovered as part of a patient's routine care.
Once eligibility is determined, enrolled participants are randomized into one of two groups:
- Group A will start with carboplatin first, given every 21 days for up to 10 cycles, then
have the option to switch to the second treatment with docetaxel every 21 days.
- Group B will start with docetaxel first, given every 21 days for up to 10 cycles, then
have the option to switch to the second treatment with carboplatin every 21 days.
Both study drugs in this trial are currently FDA approved, and are given intravenously (IV)
at the participating VAMC clinical sites per institutional guidelines.
Participants are monitored for health and body function, cancer progression, toxicity and
life quality at every visit during the trial and at an end of treatment visit (28 days after
completion of the trial or after withdrawal). For participants who respond well to treatment
during the trial, additional treatment cycles may be added and the study can be extended.
Participants who experience intolerable toxicity, cancer progression, or whose doctors decide
to change treatment, will either be switched to the opposite study drug or withdrawn from the
study.
This important trial is designed to compare response rate and duration of response using
carboplatin compared to docetaxel in patients who have mCRPC which contains DNA repair gene
mutations.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Treatment Arm 1 - Carboplatin to Docetaxel | Active Comparator | Participants are administered carboplatin AUC 5 IV first, which is administered Cycle-1, Day-1, and then every 21 days as first line therapy. For second line (crossover), docetaxel is administered 75 mg/m2 IV every 21 days thereafter. | |
| Treatment Arm 2 - Docetaxel to Carboplatin | Active Comparator | Participants are administered docetaxel 75 mg/m2 IV first, which is administered Cycle-1, Day-1, and then every 21 days as first line therapy. For second line (crossover), carboplatin is administered AUC 5 IV every 21 days thereafter. | |
Eligibility Criteria
Inclusion Criteria:
- Signed study informed consent form (ICF)
- Male age > 18 years
- Diagnosis of prostate cancer (pure small-cell histology or pure high-grade
neuroendocrine histology are excluded; neuroendocrine differentiation is allowed)
- 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
- mCRPC as defined by serum testosterone < 50 ng/ml (for patients on GnRH analogues or
antagonists) and one of the following:
- PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions
at least 1 week apart
- Evaluable disease progression by modified RECIST 1.1 (Response Evaluation
Criteria in Solid Tumors)
- Progression of metastatic bone disease on bone scan, CT or MRI with > 2 new
lesions
- Prior therapy with abiraterone acetate, and/or enzalutamide
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 (See Appendix 3,
ECOG Grading Scale)
- Results of previous standard DNA testing, or previous research testing, which confirms
BRCA1, BRCA2, or PALB2 mutations (see Introduction section 2 for study design and
previous research on targeted therapy) from primary, metastatic tumor or circulating
tumor DNA, or pathogenic/likely pathogenic germline variant as assessed by a CLIA
certified laboratory level assay for DNA sequencing.
Exclusion Criteria:
- Currently receiving active therapy for other neoplastic disorder(s)
- Concurrent enrollment in another clinical investigational drug or device study
- Morphologic evidence of neuroendocrine or small cell carcinoma of the prostate
- Prior treatment with platinum or docetaxel chemotherapy for CRPC
- Parenchymal brain metastasis
- 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 within 30 days of Cycle-1
- Presence of dementia, psychiatric illness, and/or social situations limiting
compliance with study requirements or understanding and/or giving of informed consent
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | Accepts Healthy Volunteers |
Primary Outcome Measures
| Measure: | Progression-free survival (PFS-1L) defined as the time interval between randomization and first documented disease progression or death due to any cause reported during, or after, first-line treatment. |
| Time Frame: | 10 cycles for each treatment or progression, whichever comes first (cycles are every 21 days) |
| Safety Issue: | |
| Description: | Progression free survival (PFS) by bone scan or measurable disease, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) to initial therapy (PFS-1L) with carboplatin vs. docetaxel |
Secondary Outcome Measures
| Measure: | time interval between randomization and second documented disease progression during or after second-line or death (due to any cause) |
| Time Frame: | Through duration of the study, up to six years |
| Safety Issue: | |
| Description: | Progression-free survival combined, a composite endpoint defined as the time interval between randomization and second documented disease progression reported during or after second-line or death due to any cause |
| Measure: | PSA measurements/response |
| Time Frame: | Through duration of the study, up to six years |
| Safety Issue: | |
| Description: | To assess PSA response to initial therapy with carboplatin vs. docetaxel |
| Measure: | PSA measurements/response |
| Time Frame: | Through duration of the study, up to six years |
| Safety Issue: | |
| Description: | To assess PSA response duration to second line therapy with docetaxel vs carboplatin |
| Measure: | Grade 3 and 4 toxicities in first and second-line setting |
| Time Frame: | Through duration of the study, up to six years |
| Safety Issue: | |
| Description: | To assess Grade 3 and 4 toxicities for each regimen in the first- and second-line setting |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | VA Office of Research and Development |
Trial Keywords
- metastatic prostate cancer
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