Utilizing A Genomic Sig for "BRCAness" to Eval the Efficacy of Satraplatin in Men With Met. Castration Resistant Prostate Ca

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wiliam K. Oh, M.D., Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01289067
First received: January 7, 2011
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Satraplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Oh, William K., M.D.:

Primary Outcome Measures:
  • To determine the efficacy of Satraplatin as second line therapy in men with CRCP [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Patients with good tolerance of treatment who have a 30% PSA decline from their pre-treatment level withtin 3 months of treatment initiation will be considered responders provided objective tumor measurements are stable or also demonstrate response.


Secondary Outcome Measures:
  • To assess response rates [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Response will be evaluated in this study using PSA (Prostate-Specific Antigen) measurements (every 4 weeks) and by using the Response Evaluation Criteria in Solid Tumors(RECIST) every 2 cycles (or approximately every 9 weeks). PSA response will be measured as the percentage of change in PSA from baseline to 12 weeks in therapy (or earlier if patients discontinue therapy prior to 12 weeks) as well as the maximum decline in PSA that occurs at any point during treatment. PSA decline will be reported globally using a waterfall plot.

  • Progression Free Survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Progression Free Survival is measured from the time of the initiation of therapy until the first dat that recurrent or progressive disease is objectively documentsd. Progression is a composite endpoint that can be based upon PSA, objective measures of disease, symptoms or death.

  • Overall Survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Patients will be 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.


Enrollment: 13
Study Start Date: December 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Satraplatin, Single Arm Drug: Satraplatin
Satraplatin 80mg/m2 day 1-5 every 35 days Prednisone 5 mg twice daily every 35 days
Other Name: JM-118

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289067

Locations
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029
Sponsors and Collaborators
Oh, William K., M.D.
Investigators
Principal Investigator: William K Oh, M.D. Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Wiliam K. Oh, M.D., Chief, Division of Hematology/Medical Oncology, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01289067     History of Changes
Other Study ID Numbers: 10-1222, Prostate Cancer Foundation
Study First Received: January 7, 2011
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Oh, William K., M.D.:
Metastatic
Castration Resistant
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Satraplatin
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014