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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01289067
• Other study ID #: GCO 10-1222
• Secondary ID: Prostate Cancer
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2011
• Last updated: January 16, 2018
• Start date: December 2010
• Est. completion date: May 2013

Study information

• Verified date: January 2018
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Satraplatin
Satraplatin 80mg/m2 day 1-5 every 35 days Prednisone 5 mg twice daily every 35 days

Locations

Country	Name	City	State
United States	Mount Sinai Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
William K. Oh	Prostate Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	3 months
Secondary	Number of Days to Maximum Decline in PSA	Response rate - Maximum decline in PSA that occurs during treatment.	baseline and 3 months
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.	up to 2 years
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.	24 months