Clinical trial NCT01289067: Utilizing A Genomic Sig for "BRCAness" to Eval the Efficacy of Satraplatin in Men With Met. Castration Resistant Prostate Ca
Official title: Predicting Response to Platinum Chemotherapy in Metastatic Castration Resistant Prostate Ca(mCRPC)Using a Genomic Signature for "BRCAness": A Phase II Prospective Open Label Clinical Trial of Satraplatin in Men With mCRPC Who Have Progressed on Docetaxel
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Metastatic
Castration Resistant
Prostate Cancer
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Prostate Cancer Foundation
First posted: 2011-02-03
Enrollment: 13
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of Satraplatin as Second Line Therapy in Men With CRCP
timeFrame: 3 months
Secondary outcomes:
measure: Number of Days to Maximum Decline in PSA
timeFrame: baseline and 3 months
measure: Progression Free Survival (PFS)
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: 24 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: William K Oh, M.D.
role: PRINCIPAL_INVESTIGATOR
References: