Utilizing A Genomic Sig for "BRCAness" to Eval the Efficacy of Satraplatin in Men With Met. Castration Resistant Prostate Ca
Status: | Completed |
---|---|
Conditions: | Prostate Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 2/15/2018 |
Start Date: | December 2010 |
End Date: | May 2013 |
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
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.
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.
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.
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.
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.
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