Official Title: “A Phase II Study of Satraplatin and Prednisone in Metastatic Androgen Independent Prostate Cancer (AIPC)”

RATIONALE: Drugs used in chemotherapy, such as satraplatin and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving satraplatin together with prednisone may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving satraplatin together with prednisone works in treating patients with progressive, metastatic prostate cancer.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled

Study Primary Completion Date: January 2010

OBJECTIVES:

Primary - To determine if the presence of ERCC1 variant gene polymorphism may be associated with an impact on the progression-free survival of patients with metastatic androgen-independent prostate cancer.

Secondary - To measure the overall response rate and overall survival in a post-hoc analysis. - To demonstrate the biologic effect of satraplatin in white blood cell collections and in the tumor whenever possible. - To determine the correlation of biologic or clinical effects with prostate-specific antigen (PSA) progression. - To determine the incidence of different gene polymorphisms by genotyping using polymerase-chain reaction (PCR) followed by either restriction fragment length polymorphism or direct sequencing to genotype single nucleotide polymorphisms of ERCC1, XRCC1, and PARP1. - To evaluate the correlation between genotype expression, repair pathways, and clinical events.

OUTLINE: Patients receive oral satraplatin once daily on days 1-5 and oral prednisone twice daily on days 1-35. Courses repeat every 35 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically and analyzed for genotyping of ERCC1 and other gene polymorphisms via polymerase chain reaction (PCR).

Intervention(s) in this Clinical Trial

• Drug: prednisone
• Drug: satraplatin
• Procedure: gene expression analysis
• Procedure: pharmacological study
• Procedure: polymerase chain reaction
• Procedure: polymorphism analysis

Primary Measures

• Progression-free survival
  • Safety Issue?: No

Secondary Measures

• Overall survival
  • Safety Issue?: No
• Toxicity
  • Safety Issue?: Yes
• Genotyping
  • Safety Issue?: No
• Prostate-specific antigen
  • Safety Issue?: No
• Molecular endpoints
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer, meeting the following criteria:
• Metastatically progressive disease
• Androgen-independent disease
• Patients whose pathology specimens are not available may be enrolled in the trial provided the patient has a clinical course consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis
• Must have radiographic evidence of disease by CT scan or bone scan that has continued to progress after primary treatment despite hormonal agents
• Progression requires that a measurable lesion is expanding, new lesions have appeared, and/or the prostate-specific antigen (PSA) is continuing to rise on successive measurements
• Patients on flutamide for the prior 6 months must have disease progression at least 4 weeks after withdrawal
• Patients on bicalutamide or nilutamide must have progression at least 6 weeks after withdrawal
• Must have progressive disease after 1 prior cytotoxic chemotherapy but may have had no more than 1 previous cytotoxic chemotherapeutic line
• Multiple courses of a taxane-based regimen may count as a single regimen
• Multiple courses of a non-taxane agent or a combination chemotherapy regimen may count as a single regimen
• Patients who have not undergone bilateral surgical castration must continue suppression of testosterone production by appropriate usage of GnRH agonists
• No known active brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-2
• Life expectancy > 3 months
• Leukocytes ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limits of normal (ULN) (except for patients with Gilbert disease)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• No ongoing malignancies requiring active therapy
• Fertile patients must use effective contraception
• Must be able to swallow capsules
• Able to understand and sign an informed consent

Exclusion criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to satraplatin or prednisone
• Uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active serious infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Psychiatric illness/social situations that would limit patient compliance with study requirements
• HIV positivity
• Diseases where corticosteroids are contraindicated, (e.g. , active gastric or duodenal ulcer, or poorly-controlled insulin dependent diabetes)
• Well-controlled insulin-dependent diabetes mellitus allowed provided the patient understands that their glucose levels will increase which will require their insulin dose to be adjusted

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics
• Recovered from all prior therapy
• Concurrent bisphosphonates allowed provided the patient has been previously receiving that drug
• If patients are not currently receiving bisphosphonates at the time of study enrollment, bisphosphonates may be started in course 2
• Patients who require hematopoietic growth factor support (e.g., epoetin alfa or darbepoetin), but not myeloid growth factors (i.e., filgrastim [G-CSF], sargramostim
• [GM-CSF], or other bone marrow stimulants) (except after course 1 if clinically indicated), NSAIDs, and other maintenance medications prior to study entry are allowed to continue their supportive therapies
• Patients on chronic stable steroids (e.g., no more than 10 mg prednisone/day) for a non-cancerous condition allowed
• Prior samarium-153 allowed

Exclusion criteria:

• Prior satraplatin or other platinum-containing compounds
• Prior radiotherapy to > 30% of the bone marrow
• Prior strontium chloride Sr 89, rhenium Re186, or rhenium Re188
• Prior major gastrointestinal surgery or pathology likely to influence absorption of oral medications (i.e., bypass surgeries, Whipple's procedure, or any surgery that would impair reliable absorption of oral drugs)
• Concurrent prophylactic growth factor support
• Concurrent anticancer treatment with chemotherapy, radiotherapy, major surgical procedures for prostate cancer, or nonprotocol-related immunotherapy
• Other concurrent investigational or commercial agents or therapies other than those used for this study with the intent to treat the patient's malignancy

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

William Dahut, MD Principal Investigator National Cancer Institute (NCI)  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00634647

Study ID Number: CDR0000589015

ClinicalTrials.gov Identifier: NCT00634647

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database