Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, PSA Progression, Stage IV Prostate Cancer
Conditions
Brief summary
This pilot clinical trial studies docetaxel and carboplatin in treating patients with castration resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) and contains inactivated genes in the BRCA 1/2 pathway. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed description
OUTLINE: Patients receive docetaxel intravenously (IV) over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGCarboplatin
Given IV
DRUGDocetaxel
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
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 carcinoma of the prostate (excluding neuroendocrine differentiation or squamous 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 rising PSA when serum testosterone \< 50 ng/ml (note: current testosterone results are not required if the potential subject has not missed any GnRH analogue/antagonist doses since their last result was received) 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 (Response Evaluation Criteria in Solid Tumors) * Progression of metastatic bone disease on bone scan with \> 2 new lesions * Prior therapy with abiraterone, enzalutamide and/or docetaxel; there is no limit to the number of prior treatment regimens * Presence of metastatic disease on scans * 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) * Absolute neutrophil count \>= 1.5 x 10\^9 cells/L * Hemoglobin (Hgb) \>= 9.0 g/dL * Platelets \>= 100,000 x 10\^9/L * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal (ULN) * Total bilirubin levels =\< 1.5 x ULN * Patients must have clear and documented evidence of biallelic inactivation BRCA1, BRCA2 or ATM by sequencing, for example University of Washington (UW)-Oncoplex, SU2C, or Foundation One testing and/or patients with clearly deleterious mutations of other genes involved in homologous DNA repair (e.g., partner and localizer of BRCA2 \[PALB2\], BRCA1-interacting protein 1 \[BRIP1\], etc.) by sequencing via UW-Oncoplex, SU2C, or Foundation One testing may be included at the investigator's discretion
Exclusion criteria
* Currently receiving active therapy for other neoplastic disorders * Histologic evidence of neuroendocrine or small cell carcinoma of the prostate * Known 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, if done * Treatment with an investigational therapeutic within 30 days of cycle 1 * Patients with dementia/psychiatric illness/social situations limiting compliance with study requirements or understanding and/or giving of informed consent are not eligible * Any medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained are not eligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With PSA Decline by 50% From Baseline | Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication | Proportion of patients with PSA decline by 50% from baseline according to Prostate Cancer Working Group 2 (PCWG2) criteria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Docetaxel, Carboplatin) Patients receive docetaxel IV over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 courses in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Docetaxel: Given IV
Laboratory Biomarker Analysis: Correlative studies | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Treatment (Docetaxel, Carboplatin) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 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 | 1 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 | 13 Participants |
| Region of Enrollment United States | 14 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 14 |
| other Total, other adverse events | 5 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Proportion of Patients With PSA Decline by 50% From Baseline
Proportion of patients with PSA decline by 50% from baseline according to Prostate Cancer Working Group 2 (PCWG2) criteria
Time frame: Until disease progression or unacceptable toxicity, assessed up to 35 days after the last dose of study medication
Population: Patients treated with docetaxel and carboplatin.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Docetaxel, Carboplatin) | Proportion of Patients With PSA Decline by 50% From Baseline | achieved PSA50 | 9 Participants |
| Treatment (Docetaxel, Carboplatin) | Proportion of Patients With PSA Decline by 50% From Baseline | did not achieve PSA50 | 5 Participants |
Comparison: The primary efficacy endpoint was percent patients achieving PSA decline of 50% or more from baseline (PSA50), assessed in the time prior to disease progression, unacceptable toxicity or 1 year after the last study medication. The historical comparison was PSA50 of 26%. The target response rate was 60%. The study followed an optimal two-stage Simon design (Simon, 1989) where the null hypothesis that the true PSA response rate PSA50 was 0.26 was tested against a one-sided alternative.