Prostate Cancer
Conditions
Keywords
Metastatic, Castration Resistant, Prostate Cancer
Brief summary
The purpose of the study is to test genes for BRCAness(BRCA\[BReast CAncer\] gene) Studying these genes could help predict which patients would benefit from treatment with satraplatin, a medication being used for subjects who have failed prior chemotherapy. All subjects will have a biopsy of metastatic lesions to measure BRCAness (a gene signature). This gene signature may be able to predict response to satraplatin and a tool will be developed to be able to screen patients likely to benefit from satraplatin. Subjects will all receive Satraplatin days 1-5 and Prednisone 5 mg twice daily every 35 days. Response rates will be evaluated every 2 cycles or approximately every 9 weeks. Patients will be considered responders if they have measurable disease meeting criteria for partial or complete response. PSA will be measured day one of each treatment cycle. Each treatment cycle is 35 days.
Detailed description
We will be developing a genomic based signature of BRCAness based on literature of genomic signatures from women with breast cancer and germline BRCA mutations.The BRCAness breast cancer signature will differentiate germline BRCA 1/2 breast cancers from standard estrogen-receptor (+) breast cancers. We will obtain a library of genomic signatures Recently these techniques have been used to develop a transcriptional signature for androgen receptor (AR) activity in men with CRPC(Castration Resistant Prostate Cancer). The investigator will apply the BRCAness breast cancer signature to pathological prostate cancer specimens to determine the percentage of patients in the overall prostate cancer population that express this signature, as well as the clinical and histological phenotype of this population. This novel prostate cancer BRCAness signature will be developed over a period of 4-6 months. This BRCAness signature has not previously been evaluated in prostate cancer patients and would be expected, based on known characteristics of BRCA mutant breast and ovarian cancers, to be more platinum-responsive. Relevant clinical data, including histology, grade, stage, size of residual tumor, recurrence, and survival, will be obtained from outpatient and inpatient charts to perform subsequent correlative studies. All patients enrolled in the phase II clinical trial with satraplatin will have pre-treatment biopsies of metastatic sites. All of the specimens will be frozen, batched and stored as previously described. We anticipate that all patients will be enrolled 16 months from when the trial opens. When the last patient is enrolled in the trial and all of the metastatic biopsies have been collected, they will be shipped in bulk on dry ice to laboratory for RNA(ribonucleic acid) isolation, RNA quality assessment and processing, microarray hybridization, microarray data quality assessment, and BRCAness prostate cancer signature application. Frozen biopsies will be processed for microarray analysis using laser capture microdissection and RNA amplification using adaptations of previously published methods. The application of the prostate cancer BRCAness signature will take place over two months.
Interventions
DRUGSatraplatin
Satraplatin 80mg/m2 day 1-5 every 35 days Prednisone 5 mg twice daily every 35 days
Sponsors
Prostate Cancer Foundation
William K. Oh
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
1. Patients must have histologically confirmed adenocarcinoma of the prostate. 2. Radiographic evidence of metastatic disease (Bone scan, CT(Computerized Tomography) scan, or MRI(Magnetic Resonance Imaging) are acceptable) amenable to image-guided biopsy. 3. Castrate levels of testosterone (testosterone \<50 ng/dL) on androgen deprivation therapy (ADT). LHRH(luteinizing hormone releasing hormone)agonist therapy must continue while on study unless patient has previously undergone an orchiectomy. 4. The patient must have discontinued antiandrogens (bicalutamide, flutamide or nilutamide) 30 days prior to baseline PSA. 5. Progression on at least one line of a prior docetaxel-based chemotherapy. 6. Patients must have adequate organ and marrow function as defined below: * Absolute neutrophil count \>1,500/μl * Platelets \>100,000/μl * GFR(glomerular Filtration Rate) \>30 ml/min * ALT(Alanine transaminase) and AST(Aspartate transaminase) ≤ 2.5 X upper limit of normal (ULN) or ≤ 5 X ULN in patients with liver metastasis 7. Age \> 18 years 8. Ability to take oral medications (pills must be swallowed whole) 9. ECOG (Eastern Cooperative Oncology Group) performance status 0-2 10. Ability to understand and the willingness to sign a written informed consent document 11. Patients must be willing to undergo an image-guided biopsy of a metastatic site on at least one occasion. 12. Patient agrees to utilize contraception while enrolled in the trial
Exclusion criteria
1. Patients who have received prior treatment with a platinum chemotherapy. 2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), history of symptomatic congestive heart failure (NYHC (New York Heart Association Classification) III), unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT(Super ventricular tachycardia)or any VT(ventricular tachycardia), or psychiatric illness/social situations that would limit compliance with study requirements. 3. Patients with a medical contraindication to image-guided biopsies 4. Patients with a severe allergic reaction to satraplatin compounds. 5. Has a history of a prior malignancy with the exception of the following: adequately treated basal cell or squamous cell skin cancer, or other cancers for which the subject has been disease-free for at least 5 years. 6. Has had radiation therapy within 30 days prior to being registered for protocol therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Satraplatin as Second Line Therapy in Men With CRCP | 3 months | Patients with good tolerance of treatment who have a 30% PSA decline from their pre-treatment level within 3 months of treatment initiation will be considered responders provided objective tumor measurements are stable or also demonstrate response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days to Maximum Decline in PSA | baseline and 3 months | Response rate - Maximum decline in PSA that occurs during treatment. |
| Progression Free Survival (PFS) | up to 2 years | Progression Free Survival is measured from the time of the initiation of therapy until the first date that recurrent or progressive disease is objectively documented. Progression is a composite endpoint that can be based upon PSA, objective measures of disease, symptoms or death. Time to disease progression. |
| Overall Survival | 24 months | Patients followed for a minimum of 24 months or until death. Patients and/or their family members will be contacted via telephone calls or certified letter. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in December 2010. Thirteen (13) patients from Mount Sinai Medical Center were enrolled to the study between January 27, 2011 and March 7, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Satraplatin, Single Arm Satraplatin: Satraplatin 80mg/m2 day 1-5 every 35 days Prednisone 5 mg twice daily every 35 days | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Satraplatin, Single Arm |
|---|---|
| Age, Continuous | 69 years |
| Gleason Score Gleason 7 | 4 participants |
| Gleason Score Gleason 8 | 5 participants |
| Gleason Score Gleason 9 | 4 participants |
| Metastasis site Bone and Lymph Node | 1 participants |
| Metastasis site Bone and Visceral | 3 participants |
| Metastasis site Bone, Lymph Node, and Visceral | 2 participants |
| Metastasis site Bone only | 6 participants |
| Metastasis site Lymph Node and Visceral | 1 participants |
| Metastasis site Lymph Node only | 4 participants |
| Metastasis site Visceral only | 0 participants |
| PSA | 71.67 ng/ml |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Efficacy of Satraplatin as Second Line Therapy in Men With CRCP
Patients with good tolerance of treatment who have a 30% PSA decline from their pre-treatment level within 3 months of treatment initiation will be considered responders provided objective tumor measurements are stable or also demonstrate response.
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Satraplatin, Single Arm | Efficacy of Satraplatin as Second Line Therapy in Men With CRCP | responders | 4 participants |
| Satraplatin, Single Arm | Efficacy of Satraplatin as Second Line Therapy in Men With CRCP | non-responders | 6 participants |
| Satraplatin, Single Arm | Efficacy of Satraplatin as Second Line Therapy in Men With CRCP | not evaluable for response | 3 participants |
Secondary
Number of Days to Maximum Decline in PSA
Response rate - Maximum decline in PSA that occurs during treatment.
Time frame: baseline and 3 months
Population: Only responders included
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Satraplatin, Single Arm | Number of Days to Maximum Decline in PSA | 165.5 days |
Secondary
Overall Survival
Patients followed for a minimum of 24 months or until death. Patients and/or their family members will be contacted via telephone calls or certified letter.
Time frame: 24 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Satraplatin, Single Arm | Overall Survival | Responders | 570 days |
| Satraplatin, Single Arm | Overall Survival | Nonresponders | 486 days |
Secondary
Progression Free Survival (PFS)
Progression Free Survival is measured from the time of the initiation of therapy until the first date that recurrent or progressive disease is objectively documented. Progression is a composite endpoint that can be based upon PSA, objective measures of disease, symptoms or death. Time to disease progression.
Time frame: up to 2 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Satraplatin, Single Arm | Progression Free Survival (PFS) | Responders | 206 days |
| Satraplatin, Single Arm | Progression Free Survival (PFS) | Nonresponders | 35 days |