A Phase II Study of Satraplatin and Prednisone in Metastatic Androgen Independent Prostate Cancer (AIPC)
- Satraplatin is an oral, third-generation platinum analog that has recently been shown
to increase prostatic specific antigen (PSA) decline rates and progression-free
survival in hormone-resistant prostate cancer.
- Satraplatin acts by binding to deoxyribonucleic acid (DNA) forming intra- and
interstrand cross links (DNA adducts), resulting in cell-cycle arrest in G2 phase and
eventual apoptosis. One of the mechanisms that bring about resistance to platinum-based
chemotherapy is removal of the platinum-DNA adducts by DNA repair pathways, called
nucleotide excision repair (NER) and base excision repair (BER) pathways.
- Polymorphisms in the DNA repair genes causing impaired NER and BER capability has
recently been shown in some cancers, including head and neck squamous cell carcinoma,
non-small cell lung carcinoma, and ovarian carcinoma to predict better treatment
outcome and response to platinum treatment.
- Primary objective of this single arm study is to determine if the presence of ERCC1
variant gene polymorphism which is involved with DNA damage repair may be associated
with an impact on the progression-free survival of patients with metastatic prostate
- Secondary objectives of this study includes demonstration of biologic effect by the
drug satraplatin in the patient and in the tumor whenever possible, by obtaining tissue
biopsy and white blood cell collections, to determine correlation of biologic or
clinical effects with PSA progression, evaluate correlations between genotype
expression, repair pathways and clinical events, and obtain laboratory correlates which
will include pharmacogenetic analysis of prostate cancer patients with genotyping using
Polymerase chain reaction (PCR) followed by either restriction fragment length
polymorphism or direct sequencing to genotype single nucleotide polymorphisms of ERCC1,
x-ray repair cross-complementing protein 1 (XRCC1), and poly (ADP-ribose) polymerase 1
- Patients with metastatic androgen-independent prostate cancer.
- Had docetaxel-based chemotherapy, but no more than 1 previous cytotoxic chemotherapy
- Good organ function.
- Phase II trial with single stage design and a planned accrual of 66 patients.
- Progression-free survival will be determined using a Fisher's exact test.
- Will treat all enrolled patients with oral satraplatin 80 mg/m^2 dose on days 1-5 of
every 35-days cycle plus Prednisone 5 mg twice daily every 35 days.
- Genotyping will be performed after the first 20 patients to determine if the proportion
for wild-type ERCC1 and variants follow a 20:80 split.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression Free Survival.
Time between the start of therapy and progression. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive Disease is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
William L Dahut, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Associates in Oncology and Hematology||Rockville, Maryland 20850|