Clinical trial NCT00634647
Conditions: Prostate Cancer Genetic Polymorphism
Keywords: Chemotherapy Pharmacokinetics Gene Polymorphisms Prostate Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2008-02-19; Completion date: 2012-05-01
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

Satraplatin is an experimental drug that may be of benefit to patients with prostate cancer.

Prednisone is approved for treating prostate cancer.

The gene excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) helps repair cell damage caused by satraplatin. It is possible that patients who have a variant of this gene will not benefit from treatment with satraplatin because the drug will not be able to damage the cancer cells effectively.

Objectives:

To determine if satraplatin may help treat prostate cancer in patients with certain variants of the ERCC1 gene.

Eligibility:

Patients with advanced androgen-independent prostate cancer whose disease has not responded to hormonal therapy or at least one type of chemotherapy and whose x-rays, scans or other tests have shown their cancer to be spreading.

Design:

Participants have a blood test to determine if they have a variant of the ERCC1 gene.

Participants take satraplatin by mouth every day for 5 consecutive days out of every 35 days and prednisone by mouth every day. These 35-day treatment cycles may continue for 6 months or longer, depending on the benefits and side effects of the treatment.

During the treatment period, patients undergo the following tests and procedures:

* Blood tests on days 1 of the treatment cycle.
* Weekly blood draws for the first 3 treatment cycles.
* Imaging studies (e.g., bone scans, computed tomography (CT) scans) every two cycles to determine the response to treatment.
* Surgical or medical suppression of testosterone in patients whose cancer cells continue to grow due to exposure to the hormone....

Detailed description:
Background:

* 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.

Objectives:

* 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 cancer.
* 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 (PARP1).

Eligibility:

* Patients with metastatic androgen-independent prostate cancer.
* Had docetaxel-based chemotherapy, but no more than 1 previous cytotoxic chemotherapy line.
* Good organ function.

Design:

* 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.

Arms: arm 1: satraplatin - 80 mg/m\^2 days 1-5 of every 35 day cycle prednisone - 5 mg twice daily every 35 days
Interventions: intervention 1: Satraplatin intervention 2: prednisone
Intervention descriptions: intervention 1: 80 mg/m\^2 days 1-5 of every 35 day cycle intervention 2: 5 mg twice daily every 35 days

Protocol documents:
Prot_ICF_000.pdf: 


Version date: 5-10-11 
 
1 
 
NCI Protocol #: 08-C-0074 
 
TITLE:  A Phase II Study of Satraplatin and Prednisone in metastatic androgen independent prostate 
cancer (AIPC) 
 
Abbreviated Title:                Satraplatin in Prostate Cancer  
 
Coordinating Center: 
Medical Oncology Branch 
 
 
National Cancer Institute 
 
Principal Investigator: 
William L. Dahut, MD 
                                                Medical Oncology Branch 
                                                National Cancer Institute 
 
 
Building 10, Rm 12N226 
 
 
9000 Rockville Pike 
 
 
Bethesda, MD 20892 
 
 
301-435-8143 
 
 
FAX: 301-435-3854 
 
 
dahutw@mail.nih.gov 
 
Statistician: 
 
 
Protocol Chair: 
Seth Steinberg, PhD 
William D. Figg, PharmD 
Biostatistics and Data Management Section 
Clinical Pharmacology Program 
National Cancer Institute 
National Cancer Institute 
6116 Executive Blvd, Rm 702 
Bldg 10, Rm 5A01 
Bethesda, MD 20892 
9000 Rockville Pike 
301-496-9502                                                             Bethesda, MD 20892 
Fax: 301-402-1259                                                     301-402-3622 
steinbes@mail.nih.gov 
 
 
 
 
 
 
Fax: 301-402-8606 
 
 
 
 
 
 
 
      wdfigg@helix.nih.gov 
 
Associate Investigators:    
James Gulley, M.D., Ph.D., LTIB/CCR/NCI 
Philip M. Arlen, M.D., LTIB/CCR/NCI 
Howard Parnes, M.D., DCP/PUCR/NCI 
John Wright, MD, CTEP/NCI 
Anna Couvillon, NP, MOB/CCR/NCI/NIH 
Ravi Madan, M.D., LTIB/CCR/NCI 
 
Associate Investigators: No Clinical Decisions 
Melony Beatson, R.N., MOB/CCR/NCI 
David Kohler, Pharm.D., PD/CCR/NIH 
Douglas K. Price, PhD MOB/CCR/NCI 
 
Research Contact: 
 
Melony Beatson, R.N., MOB/CCR/NCI 


Version Date: 05-10- 2011 
2 
 
Participating Center:  
 
Principal Investigator: Manish Agrawal, MD 
Institution: Associates in Oncology and Hematology 
Address: 9707 Medical Center Drive Suite #300  
Rockville, Maryland 20850  
Tel: 301-424-6231 
Email: magrawal@aohmd.com 
 
IRB Contact: Debarati Dasgupta, MS, CIP IRB Administrator  
FWA Number: FWA00000969 (Shady Grove Adventist Hospital)  
 FWA00005579 (Associates in Oncology and Hematology)  
Address: Adventist HealthCare, Inc. System Quality  
1801 Research Blvd, Suite #200 Rockville. MD 20850  
Tel: 240-826-5739  
Email: DDasgupt@adventisthealthcare.com 
 
 
Study Conducted by: 
Genitourinary/Gynecologic Malignancies Clinic 
 
Medical Oncology Branch 
 
National Cancer Institute 
 
Clinical Center (Bldg 10) 
 
National Institutes of Health 
 
Bethesda, MD 20892 
 
Drug Supplier and Manufacturer: 
 Agennix, Inc., 
 
101 College Road East  
 
Princeton, NJ 08450 
 
Tel: (609)524-1000 
 
Fax: (609)524-1050 
 
IND Sponsor: 
 
 
 
 
 
 
 
 
 
 
 
William L. Dahut, MD 
                                                 
 
 
 
Medical Oncology Branch 
                                                 
 
 
 
National Cancer Institute 
 
 
 
 
 
 
Building 10, Rm 12N226 
 
 
 
 
 
 
9000 Rockville Pike 
 
 
 
 
 
 
Bethesda, MD 20892 
 
 
 
 
 
 
301-435-8143 
 
 
 
 
 
 
FAX: 301-435-3854 
 
 
 
 
 
 
dahutw@mail.nih.gov 
 
 
 
 
 
 
 
Protocol Version Date: 
 May 10, 2011 
Amendment F 
 
IND Satraplatin 101,655


Version date: 5-10-11 
3 
Prior to Day 1 
Baseline Evaluation 
History and Physical Exam 
Laboratory Evaluation 
PSA 
Electrocardiogram Baseline 
Pathologic Confirmation 
Tumor Biopsy (if applicable) 
Scans: 
 CT (chest, abdomen, pelvis) 
 Bone Scan 
 Chest X-ray 
Days 1-5 (Every Cycle) 
Anti-emetic, oral administration 
Satraplatin 80 mg/m2 (rounded to the nearest 10), oral 
administration. 
Days 1-35 (Every Cycle) 
Prednisone 5 mg, twice daily, oral administration. 
(Note* On days 1-5, prednisone will be taken 2 hours prior 
to Satraplatin dose.) 
Every Cycle (+/- 4 days) 
Follow- up evaluation 
History and Physical Exam 
Laboratory evaluation 
PSA 
Every 2 Cycles (+/- 4 days) 
CT Scan (only if baseline CT shows 
positive disease) 
Bone Scan 
 


Version Date: 05-10- 2011 
4 
 
Every week: 
Complete blood count with differential will be drawn (either at the Clinical Center or outside laboratory) for Cycles 1-3. If the 
Absolute Neutrophil Count (ANC) nadir is > 1.5 x 109/L and the platelet nadir is > 100 x 109/L, CBC may be drawn only on Day 1 of 
each cycle starting with Cycle 4. If the ANC is < 0.5 x 109/L and the platelet count is < 25.0 x 109/L, CBC with differential must be 
drawn at least 2 times per week or more, until resolved. 


Version date: 5-10-11 
 
5 
 
PRÈCIS 
 
Background: 
g
 Satraplatin is an oral, third-generation platinum analog that has recently been shown to 
increase PSA decline rates and progression-free survival in hormone-resistant prostate 
cancer.  
 Satraplatin acts by binding to 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. 
Objectives:   
j
 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 cancer. 
 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, XRCC1, and 
PARP1. 
Eligibility: 
g
 Patients with metastatic androgen-independent prostate cancer 
 Had docetaxel-based chemotherapy, but no more than 1 previous cytotoxic chemotherapy 
line 
 Good organ function 
Design: 
g
 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/m2 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 


Version Date: 05-10- 2011 
6 
 
TABLE OF CONTENTS 
1 
INTRODUCTION ................................................................................................................ 10 
1.1 
STUDY OBJECTIVES .......................................................................................................... 10 
1.1.1 
Primary Objective ..................................................................................................... 10 
1.1.2 
Secondary Objectives ................................................................................................ 10 
1.2 
BACKGROUND AND RATIONALE ....................................................................................... 10 
1.2.1 
Androgen-Independent Prostate Cancer (AIPC) ...................................................... 10 
1.2.2 
Satraplatin................................................................................................................. 11 
1.2.3 
Prednisone ................................................................................................................ 18 
1.2.4 
Background on DNA gene polymorphisms and rationale for use of satraplatin in 
AIPC 
19 
1.2.5 
Excision repair cross-complementation group 1 (ERCC1) ...................................... 19 
1.2.6 
Other DNA repair gene polymorphisms ................................................................... 21 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT ................................................... 22 
2.1 
ELIGIBILITY CRITERIA ...................................................................................................... 22 
2.1.1 
Inclusion Criteria ...................................................................................................... 22 
2.1.2 
Exclusion Criteria ..................................................................................................... 23 
2.2 
RESEARCH ELIGIBILITY EVALUATION .............................................................................. 24 
2.2.1 
Imaging Studies (Baseline- obtained within 4 weeks prior to enrollment): ............. 24 
2.2.2 
Laboratory Evaluation (Baseline- obtained within 16 days prior to enrollment) .... 24 
2.3 
PATIENT REGISTRATION ................................................................................................... 24 
3 
STUDY DESIGN .................................................................................................................. 25 
3.1 
DRUG ADMINISTRATION ................................................................................................... 25 
3.1.1 
Satraplatin administration ........................................................................................ 25 
3.1.2 
Prednisone administration ........................................................................................ 26 
3.2 
TREATMENT MODIFICATIONS ........................................................................................... 26 
3.2.1 
Dose modification for satraplatin: ........................................................................... 26 
3.2.2 
Hematologic Toxicity: ............................................................................................... 27 
3.2.3 
Hematologic toxicity Dose adjustments and reductions ........................................... 27 
3.2.4 
Retreatment guidelines: ............................................................................................ 28 
3.2.5 
Dose Modification for Prednisone: .......................................................................... 28 
4 
CORRELATIVE STUDIES ................................................................................................ 29 
4.1 
TISSUE ANALYSIS.............................................................................................................. 29 
4.1.1 
Accessible tumor biopsy ............................................................................................ 29 
4.2 
LEUKOCYTE ANALYSIS ..................................................................................................... 29 
4.3 
GENOTYPING ANALYSIS: ................................................................................................... 30 
4.3.1 
Patient Population and Scope of Studies .................................................................. 30 
4.3.2 
Blood sample collection ............................................................................................ 30 
4.4 
PROTOCOL COMPLETION/SAMPLE DESTRUCTION ............................................................. 31 
5 
PROTOCOL EVALUATION ............................................................................................. 32 
5.1 
BASELINE EVALUATION ........................................................................................... 32 
5.2 
LABORATORY STUDIES (SEE ALSO APPENDIX C – STUDY CALENDAR) ............................. 32 


Version Date: 05-10- 2011 
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5.3 
IMAGING SUTIDES ...................................................................................................... 32 
6 
CONCURRENT THERAPIES ........................................................................................... 32 
6.1 
NAUSEA ............................................................................................................................ 32 
6.2 
DIARRHEA ........................................................................................................................ 32 
6.3 
ANALGESICS FOR PAIN ...................................................................................................... 33 
6.4 
CONCURRENT USE OF BISPHOSPHONATES WILL BE ALLOWED ........................................... 33 
7 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY 
CRITERIA................................................................................................................................... 33 
7.1 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY ...................................................... 33 
7.2 
POST TREATMENT EVALUATION ....................................................................................... 33 
7.3 
OFF STUDY CRITERIA: ...................................................................................................... 33 
7.3.1 
Off-Study Procedure: ................................................................................................ 34 
8 
DATA COLLECTION ........................................................................................................ 34 
8.1 
PATIENT RECORDS AND QUALITY ASSURANCE ................................................................ 34 
8.1.1 
Drug Accountability .................................................................................................. 34 
8.2 
EVALUATION OF DISEASE ................................................................................................. 34 
8.2.1 
Definitions ................................................................................................................. 35 
8.2.2 
Guidelines for Evaluation of Measurable Disease ................................................... 35 
8.3 
RESPONSE CRITERIA ......................................................................................................... 36 
8.3.1 
Evaluation of target lesions ...................................................................................... 36 
8.3.2 
Evaluation of non-target lesions ............................................................................... 37 
8.3.3 
Evaluation of best overall response .......................................................................... 37 
8.3.4 
Confirmatory Measurement/Duration of Response .................................................. 38 
8.3.5 
Biochemical Response Criteria –PSA measurements (PSA Consensus Criteria) [68]
 
38 
8.4 
TOXICITY CRITERIA .......................................................................................................... 39 
9 
STATISTICAL ANALYSIS ................................................................................................ 39 
9.1 
SAMPLE SIZE/ACCRUAL RATE .......................................................................................... 41 
9.2 
STRATIFICATION FACTORS ............................................................................................... 41 
9.3 
ANALYSIS OF SECONDARY ENDPOINTS ............................................................................. 41 
10 HUMAN SUBJECTS PROTECTIONS ............................................................................. 41 
10.1 
RATIONALE FOR SUBJECT SELECTION ............................................................................ 41 
10.2 
PARTICIPATION OF CHILDREN ....................................................................................... 41 
10.3 
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS .................................................... 41 
10.4 
RISKS TO PATIENTS IN RELATION TO ANTICIPATED BENEFITS ........................................ 41 
10.5 
CONSENT PROCESS ........................................................................................................ 42 
11 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN ............................................................................................................................................ 42 
11.1 
DEFINITIONS ............................................................................................................. 42 
11.1.1 
Adverse Event ........................................................................................................ 42 
11.1.2 
Suspected adverse reaction ................................................................................... 43 


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11.1.3 
Unexpected adverse reaction................................................................................. 43 
11.1.4 
Serious ................................................................................................................... 43 
11.1.5 
Disability ............................................................................................................... 43 
11.1.6 
Life-threatening adverse drug experience ............................................................. 43 
11.1.7 
Protocol Deviation (NIH definition)...................................................................... 43 
11.1.8 
Protocol Violation (NIH definition) ...................................................................... 44 
11.1.9 
Unanticipated Problem.......................................................................................... 44 
11.2 
NCI-IRB REPORTING ................................................................................................ 44 
11.2.1 
NCI-IRB Expedited Reporting of Adverse Events, Unanticipated Problems, and 
Deaths 
44 
11.2.2 
NCI-IRB Requirements for PI Reporting of Adverse Events at Continuing Review
 
44 
11.2.3 
NCI-IRB Reporting of IND Safety Reports ............................................................ 44 
11.3 
NCI GUIDANCE FOR REPORTING EXPEDITED ADVERSE EVENTS FOR 
MULTI-CENTER TRIALS ....................................................................................................... 45 
11.4 
IND SPONSOR REPORTING CRITERIA ................................................................. 45 
11.5 
FDA REPORTING CRITERIA ................................................................................... 45 
11.5.1 
Safety Reports to the FDA (Refer to 21 CFR 312.32) ........................................... 45 
11.5.2 
FDA Annual Reports (Refer to 21 CFR 312.33) ................................................... 45 
11.5.3 
Expedited Adverse Event Reporting Criteria to the IND Manufacturer ............... 45 
11.6 
DATA AND SAFETY MONITORING PLAN ............................................................ 46 
11.6.1 
Principal Investigator/Research Team .................................................................. 46 
11.6.2 
Sponsor Monitoring Plan ...................................................................................... 47 
11.6.3 
Safety Monitoring Committee (SMC) .................................................................... 47 
12 COLLABORATIVE AGREEMENT ................................................................................. 47 
13 PHARMACEUTICAL INFORMATION .......................................................................... 47 
13.1 
SATRAPLATIN (IND 101,655) ....................................................................................... 47 
13.1.1 
Source: ................................................................................................................... 47 
13.1.2 
Chemical name and identification ......................................................................... 47 
13.1.3 
How Supplied: ....................................................................................................... 48 
13.1.4 
Storage: ................................................................................................................. 48 
13.1.5 
Stability:................................................................................................................. 48 
13.1.6 
Route of Administration: ....................................................................................... 48 
13.1.7 
Reported Adverse Events and Potential Risks: ...................................................... 48 
13.1.8 
Method of Administration:  Satraplatin should be taken with at least 120 ml to 240 
mL of clear liquids (4-8 fluid ounces) and should be given without food (no food for 2 hours 
before or 1 hour after dosing). ............................................................................................... 49 
13.1.9 
Potential Drug Interactions ................................................................................... 49 
13.1.10 
Availability............................................................................................................. 49 
13.1.11 
Agent Accountability .............................................................................................. 49 
13.2 
PREDNISONE .................................................................................................................. 50 
13.2.1 
Chemical name and identification ......................................................................... 50 
13.2.2 
How Supplied: ....................................................................................................... 50 
13.2.3 
Storage: ................................................................................................................. 50 
13.2.4 
Stability:................................................................................................................. 50 


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13.2.5 
Route of Administration: ....................................................................................... 50 
13.2.6 
Reported Adverse Events and Potential Risks: ...................................................... 50 
13.2.7 
Method of Administration:. .................................................................................... 51 
13.2.8 
Availability............................................................................................................. 51 
13.2.9 
Agent Accountability .............................................................................................. 51 
14 REFERENCES ..................................................................................................................... 52 
15 PERFORMANCE STATUS CRITERIA ........................................................................... 55 
16 APPENDIX B: PATIENTS’ PILL DIARY ....................................................................... 56 
17 APPENDIX C.  STUDY CALENDAR ............................................................................... 57 
 
 


Version Date: 05-10- 2011 
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1 
INTRODUCTION 
1.1 
Study Objectives 
1.1.1 Primary Objective 
1.1.1.1 The 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 cancer. 
1.1.2 Secondary Objectives 
1.1.2.1 Measurement of overall response rate and overall survival in a post-hoc analysis 
1.1.2.2 Demonstrate biologic effect by the drug satraplatin in the patient by white blood cell 
collections and in the tumor whenever possible, by obtaining tissue biopsy. 
1.1.2.3 Determine correlation of biologic or clinical effects with PSA progression. 
1.1.2.4 Determine the incidence in this population of AIPC patients 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. 
1.1.2.5 Evaluate correlations between genotype expression, repair pathways and clinical events. 
1.2 
Background and Rationale 
1.2.1 Androgen-Independent Prostate Cancer (AIPC) 
Prostate adenocarcinoma is the most common malignancy in American men and the second 
leading cause of cancer related deaths. 91% of prostate cancer cases are diagnosed while the 
cancer is still confined to the primary site or after the cancer has spread to regional lymphnodes 
(localized or regional stage); 5% are diagnosed after the cancer has already metastasized (distant 
stage).[1] Most patients present with localized disease and undergo potentially curative therapy, 
either radical prostatectomy (RP) or radiation therapy (RT). Although many men are cured after 
this therapy, approximately 30,000–50,000 men annually in the United States will develop 
recurrence after RP.[2-3] For most of these patients, recurrence will be defined by biochemical 
recurrence (BCR), a rise in PSA with no other documented evidence of recurrence of prostate 
cancer, otherwise known as D0 stage.[4] Most cases of BCR occur within 10 years of surgery.[5] 
However, approximately 50% of patients would develop recurrence within four years, at sites 
distant from the pelvis. [6] Thus they require systemic in addition to local therapy.  Several risk 
factors have been correlated with an increased risk of pBCR. These include pre surgery PSA 
“velocity”, pre-RP PSA, Gleason score, surgical margin status, seminal vesicle invasion, and 
pathologic stage (i.e., extension of tumor through the prostate capsule).[7] With the identification 
of active systemic agents, some patients with these risk factors are being enrolled onto trials of 
adjuvant chemotherapy or RT following RP. Androgen-deprivation therapy is the mainstay of 
treatment for metastatic prostate cancer but nearly all men with metastatic prostate cancer will 
progress to an androgen-independent phenotype and exhibit progression of disease.[8-9]  Once 
androgen-independent prostate cancer develops, responses to second-line treatment with 
alternative hormonal therapy or chemotherapies are limited, with a median overall survival of 
approximately 12 – 18 months. Androgen-independent prostate cancer(AIPC) causes significant 


Version Date: 05-10- 2011 
11 
 
morbidity, especially with symptoms of pain from bony metastasis  and mortality. [10] 
Chemotherapies have been studied extensively in the field of prostate cancer and has been 
disappointing until recently with the use of taxanes.  Among the first systemic agents studied, 
mitoxantrone was approved based on symptomatic improvement.[11-12] Subsequently, 
docetaxel was approved for the treatment of AIPC with the demonstration of improved overall 
survival of 18.9 months with the use of docetaxel and prednisone over mitoxantrone and 
prednisone with 16.5 months.[13] The search continues for delivering chemotherapy regimens 
that yield the best survival outcomes while offering the most palliation in this group of patients 
where cure is as yet unattainable.  It is for this reason that although the combination of docetaxel 
and estramustine showed similar survival advantage to docetaxel and prednisone,[14] based on 
fewer side effects, docetaxel and prednisone has become the standard of care in patients with 
metastatic AIPC. [15] However, the median time to PSA progression with taxane therapy 
remains limited to about 6-8 months, with many patients progressing thereafter[16]. There is 
currently little or no options for patients progressing on taxanes.  Therefore, there is a clear need 
for new therapeutic strategies for patients with advanced AIPC who have failed previous taxane 
chemotherapy. 
1.2.2 Satraplatin 
Satraplatin [bis-(acetato)-ammine dichloro (cyclohexylamine) platinum IV; formerly known as 
JM-216] is a third-generation orally available platinum analogue that has similar but improved 
properties with other platinum agents cisplatin and carboplatin and oxaliplatin.[17] Like other 
platinum agents, satraplatin exerts its biological activity via reactive biotransformation products 
that bind to DNA causing the inhibition of DNA replication , cell cycle arrest, and induction of 
apoptosis. Since their original discovery, platinum compounds (cisplatin, carboplatin, oxaliplatin) 
have emerged as important agents for the therapy of several human tumors including testicular,[18] 
bladder,[19] lung,[20] colorectal,[21] head and neck,[22] ovarian,[23] and cervical cancer.[23]  The 
platinum analog satraplatin is of interest as it has shown activity in some platinum resistant tumor 
models in vitro, and unlike other platinum compounds, it is absorbed when administered orally.[24]  
This is because the synthesis of the mixed amine platinum (IV) dicarboxylate dichloride series 
makes satraplatin more lipophilic and more chemically stable than other agents, offering 
improved oral bioavailability which enables satraplatin to be administered orally.  Pre-clinical 
studies with satraplatin demonstrated cytotoxic and anti-tumor activities comparable to cisplatin or 
carboplatin.[24]  Improved toxicity profiles with nephrotoxicity (as compared with cisplatin) and 
neurotoxicity(as compared with oxaliplatin) is also obviated with the substitution of the 
diaminocyclohexane (DACH) with a single cyclohexane. The asymmetrical stable ligands of 
satraplatin changes its DNA binding properties which results in a potentially different anti-tumor 
spectrum than that exhibited by cisplatin, carboplatin, and oxaliplatin. [25]   
 


Version Date: 05-10- 2011 
12 
 
Satraplatin Chemical structure 
In Vitro Activity 
In vitro studies showed cytotoxic activity in human prostate, ovarian, lung, cervical, colon, renal, 
CNS, leukemia and melanoma cell lines.  In addition, satraplatin and its active metabolite, JM-
118, showed encouraging activity in cell lines that have resistance to taxanes, mitoxantrone and 
cisplatin.  Although earlier platinum compounds have shown activity in testicular, ovarian, head 
and neck, small and non-small cell lung, colon carcinomas, the effectiveness of these compounds 
were limited because of the inherent problem with resistance.  Drug resistance to cisplatin is 
thought to occur because of decreased accumulation of cisplatin within the target cell, increased 
detoxification of platinum complexes or due to increased DNA tolerance. Satraplatin and JM-
118 were able to overcome this cisplatin resistance by virtue of the mechanisms involving 
platinum transport and DNA repair process alterations. It was also found that mechanisms which 
generally confer resistance to non-platinum based chemotherapies tend not to cause cross-
resistance with satraplatin.  IC50 values for in vitro cytotoxicity in three human prostate 
carcinoma cell lines (the androgen-sensitive LNCaP cell line, the androgen-insensitive PC-3, and 
Du-145, all at 72 hour exposures using XTT cell viability assay) are summarized in the table 
below: 
 
  
IC50 (μM) 
LNCaP 
PC-3 
Du-145 
Satraplatin 
10.9(± 0.6) 
1.4(± 0.1) 
2.8 (±0.2) 
JM-118 
0.7 (±0.6) 
0.7 (±0.1) 
0.9 (±0.2) 
JM-383 
0.7 (±0.2) 
1.1 (±0.2) 
1.3 (±0.2) 
JM-518 
2.2 (±0.7) 
1.2 (±0.3) 
0.9 (±0.1) 
Cisplatin 
3.7 (±0.4) 
1.0 (±0.2) 
1.7 (±0.3) 
Oxaliplatin 
0.3 (±0.1) 
11 (±1.0) 
1.8 (±0.5) 
Mean(±SD) 
 
 
 
Early in vitro data on hormone-dependent LNCaP cell lines showed that treatment with 
satraplatin for 42 hours with 12 μM resulted in a decrease in cell number (58% and 61% of 
control, respectively) as well as decrease in PSA protein level (58% and 61% of control, 
respectively).[26-27]  Based on the in-vitro data, PSA may serve as a surrogate marker for 
clinical response of prostate cancer to satraplatin treatment although this has not yet been 
confirmed in the clinical setting. 
In Vivo activity 
In vivo studies have demonstrated antitumor activity of satraplatin against mouse and human 
tumors transplanted in mice.  Satraplatin antitumor activity was maximal when administered 
orally as a daily x 5 treatment schedule repeated every 21 or 28 days.  A similar schedule was 
adopted for a clinical Phase III study of oral satraplatin plus prednisone called the SPARC 
(SatraPlatin Against Refractory Cancers) trial.  Satraplatin was active in mice bearing 
subcutaneously implanted hormone-independent human prostate carcinoma (PC-3) tumors when 
administered orally as two cycles of 5 daily treatment with 3 days-off dose between cycles.  
Although satraplatin effectiveness increased with increasing dose, these doses were above the 


Version Date: 05-10- 2011 
13 
 
maximum tolerated dose (MTD).  The antitumor effect of orally administered satraplatin against 
five human ovarian carcinoma xenografts (A2780, HX/110, PXN109T/C, SKOV-3 and 
OVCAR3) was compared with activities of intravenously administered cisplatin and 
carboplatin.[28-29] Maximal tumor regressions were achieved in the human ovarian carcinoma 
PXN109T/C model using cycles of 5 daily treatments repeated every 21 or 28 days, as shown in 
the table below, supporting the selection of a cycling dosing regimen for human clinical 
trials.[30-31] 
Treatment schedule 
Dose 
Max. 
BW 
Loss 
(%) 
Decedent
s 
Max Tumor Regressiona 
(Days) 
mg/kg 
mg/m2 
Single dose every 21 
days 
200 
600 
2.1 
0/6 
53%(7) 
Daily x 5 days,every 
21 days 
60 
180 
3.6 
 1/6 
17%(10) 
Daily x 5 days,every 
28 days 
60 
180 
6.3 
 1/6 
8%(10) 
Continuous daily 
dosing 
14 
42 
14 
0/10 
74%(7) 
BW=Body weight; a=% of the initial 
tumor volume 
 
 
 
Safety Pharmacology and Toxicology 
Satraplatin had no significant effects on the hERG channel at concentrations up to 100 μM.  In 
addition, satraplatin had no effect on the electrocardiogram in conscious telemetrized dogs after 
intraduodenal administration of 22.5mg/kg.  Thus, safety pharmacology study data indicate that 
satraplatin has no potential to cause cardiotoxicity.  No functions of the CNS, respiratory, renal 
and digestive systems were affected by high single doses of satraplatin. 
Toxicologic profile in pre-clinical dose-finding toxicity studies showed that the main dose-
limiting toxicity were typically hematologic, with neutropenia and thrombocytopenia.  Renal 
toxicity was limited to rats and occurred at a lesser degree compared to cisplatin treatment.  
Other toxicities include changes in the liver, GI changes in rats, increased mammary 
adenocarcinomas in rats, decreased spermatogenesis in rats, and increased infections in dogs.  
[17] Diarrhea may also be dose limiting.  No significant cardiac, renal, hepatic, or central nervous 
system (CNS) toxicity was observed. Nausea, vomiting, and diarrhea were generally mild to 
moderate, and were controlled with oral anti-emetics and antimotility drugs.  The phase I study that 
most resembles this proposed study with regard to dosing schedule administered satraplatin daily 
for 14 days. [32] In that study, the dose limiting toxicity was neutropenia, and drug-associated 
fever that was controlled with acetaminophen was also observed in 32% of patients. The dose of 
satraplatin that was chosen for later Phase 2 studies consisted of 100 to 120 mg/m2/day for 5 
consecutive days, every 21 or 28 days cycle. 
Pharmacokinetics 
Satraplatin is a platinum IV complex and the first platinum derivative in clinical development 


Version Date: 05-10- 2011 
14 
 
that is orally absorbed.  The pharmacokinetic properties of satraplatin were characterized after 
oral dosing in Balb/c mice, Sprage Dawley CD rats, Beagle dogs and Cynomolgus monkeys. 
Pivotal non-clinical pharmacokinetric studies were performed in Sprage Dawley CD rats and  
Beagle dogs, which were also the primary toxicology species.  Platinum was monitored in all 
biological samples because the presence of platinum is the prerequisite for activity. 
The concentration of platinum in plasma ultrafiltrate (PUF) was used as the primary parameter 
for calculation of satraplatin exposure and for interspecies comparison of satraplatin 
pharmacokinetics.  The concentration of platinum in PUF is a measure of the free (i.e., non-
protein bound) platinum concentration.  The protein binding of platinum was independent of 
platinum concentration and irreversible; the fraction bound increased over time up to four hours 
after oral or intravenous administration to either the rat or the dog and after oral administration to 
man.  Dosage regimen for repeat dose studies in the rat and dog were designed to simulate those 
utilized in human clinical studies, i.e., one or more cycles of five days of daily oral dosing 
followed by an off-dose period of 3-4 weeks between cycles.  In rats and dogs, after repeated 
oral doses of satraplatin, the platinum exposure in PUF increased in a dose-related, but not dose 
proportional manner up to 40 mg/kg (240mg/m2) and 13.5 mg/kg (270 mg/m2), respectively.  
Accumulation factors for platinum in PUF, within a five day dosing cycle, ranged from one (no 
accumulation) to approximately 1.6. 
Pharmacokinetic studies of Satraplatin in humans were also performed with measurement of total 
plasma platinum and PUF results at a dose of 80 mg/m2/day as summarized below in both the fed 
and fasted state: 


Version Date: 05-10- 2011 
15 
 
 
Tissue distribution studies were conducted using radiolabeled satraplatin in the mouse and by 
measurement of platinum in tissues in the mouse, dog and monkey after a single oral dose of 
satraplatin, and in the rat after single and multiple oral doses of satraplatin.  In the rat, platinum 
was present in most tissues at high concentrations after oral administration of satraplatin.  Levels 
of platinum two hours after the fifth daily oral dose were greater than 1,000ng/g tissue in 
prostate, bone marrow, kidney, lymph nodes, liver, lung, ovaries and spleen; plasma and PUF 
platinum concentrations were approximately 800 and 50 ng/ml, respectively.  The elimination 
half-life of platinum from tissues after five days of daily oral dosing was long, i.e., six days or 
longer.   
The half-life in rats has been found to be 15.5 days in whole blood, 4 days in plasma, 6.1 days in 
PUF; based on urinary excretion was approximately 90 hours. However, pharmacokinetic studies 
in patients providing accurate estimations of half-life, clearance and volume of distribution were 
not possible due to the long duration of total plasma platinum concentration observed following 
satraplatin dosing and the plasma sampling stipulated in the early protocols. 
The metabolism of satraplatin and the formation of JM-118 from satraplatin are catalyzed by 
human CYP450 oxidoreductases.  Multiple CYP450s and other NADPH-dependent, reducing 
enzymes might also be involved in the metabolism of satraplatin.  The metabolism of satraplatin 
is NADPH-dependent in pooled rat, dog and human microsomes and the rate of metabolism of 
satraplatin is similar in all species.  The potential for drug interactions due to induction of 


Version Date: 05-10- 2011 
16 
 
CYP450 isozymes is very low, and thus, satraplatin is not a known inducer of human CYP450 
isozymes in vitro.  However, satraplatin, but not JM-118, was shown to non-specifically inhibit 
numerous CYP450 isozymes in vitro.  The clinical significance of the inhibition of CYP450 
enzymes by satraplatin is unknown. 
The majority of platinum was excreted in the urine following intravenous dosing of satraplatin to 
the mouse, rat and dog.  There was a significantly higher recovery of platinum in feces than in 
urine after oral dosing, however, the increase in fecal recovery after oral dosing is primarily 
attributable to the excretion of unabsorbed drug. 
Other detailed description of nonclinical antitumor activity studies, animal toxicity, nonclinical 
pharmacokinetics, as well as clinical studies can be found in the Satraplatin Investigator Brochure.[24, 
26] 
Phase I Single Agent Satraplatin studies 
The first phase I clinical trial with the oral agent Satraplatin was initiated in Europe in 1992 
using a single dose schedule every 3 weeks.  Due to the observed nonlinear absorption with this 
trial, a 5-day daily dosing was selected for further clinical development.  An alternative schedule 
of two doses given 12 hours apart was then initiated in the UK in 1994 but was terminated prior 
to achieving maximum tolerated dose (MTD) due to non-liner pharmacokinetics.  Toxicity was 
similar to that occurring in other phase I studies including mild and short-lived nausea, vomiting, 
and diarrhea, and myelosuppression at the 250 and 350 mg/m2 dose.  Three subsequent phase I 
studies were initiated (CA-142-002 in the UK, CA142-003/9 in the US, and CA142-012 in 
Japan) using a 5-daily schedule.  Dose-limiting toxicities (DLT) for this schedule was 
thrombocytopenia, neutropenia, and diarrhea.  The MTD dose for Satraplatin given daily for 5 
days every 3 weeks ranged from 100 mg/m2day to 140 mg/m2/day.  The daily for 14 days 
schedule was also explored in study CA142-007 with the predominant dose-limiting toxicity of 
myelosuppression.  In addition, many patients had retreatment delays because of the late 
hematologic nadirs.  Other reported adverse events included: nausea, vomiting, constipation, 
stomatitis, somnolence, weight decrease, anorexia, dysphagia, asthenia, fever, headache, pain, 
insomnia, cough increased, dyspnea, and myalgia.  Fourteen patients died within 30 days of their 
last dose of Satraplatin.  Two of these deaths were attributed to study drug toxicity (one due to 
myelosuppression and one due to unknown causes).  In summary, the major DLT observed for 
the single agent phase I trials were neutropenia, thrombocytopenia and diarrhea.  Nausea and 
vomiting associated with Satraplatin treatment were generally controlled with use of 
prophylactic antiemetics. Therefore, the initial recommended phase II dosing was daily for 5 
days, every 3 to 4 weeks, at a dosage of 100 mg/m2.day to 140 mg/m2/day.    These studies and 
the DLTs are summarized herein: 
Phase I single agent satraplatin studies 
Study No. 
No. of 
patients 
Tumor 
type 
Satraplatin 
starting dose 
(mg/m2/day) 
Dose limiting toxicity 
CA142-001 
31 
Solid 
tumors 
60 (single dose) 
Not defined 


Version Date: 05-10- 2011 
17 
 
Phase I single agent satraplatin studies 
Study No. 
No. of 
patients 
Tumor 
type 
Satraplatin 
starting dose 
(mg/m2/day) 
Dose limiting toxicity 
CA142-011 
19 
Solid 
tumors 
150 (given BID) Not achieved 
CA142-002 
32 
Solid 
tumors 
30 (daily x 5) 
Myelosuppression 
CA142-
003/9 
21 
Solid 
tumors 
30 (daily x 5) 
Myelosuppression 
CA142-012 
21 
Solid 
tumors 
50 (daily x 5) 
Myelosuppression/diarrhea 
CA142-007 
47 
Solid 
tumors 
10 (daily x 14) 
Myelosuppression 
 
Clinical Experience: Satraplatin for Prostate Cancer 
 
Eight Phase II trials of single agent satraplatin given daily for 5 days every 3 to 4 weeks have been 
completed in patients with small cell lung cancer (SCLC), ovarian cancer, non-small cell lung cancer 
(NSCLC; 2 studies), prostate cancer (2 studies), breast cancer, or gastro-intestinal (GI) cancers.  
Single agent activity was noted in patients with Small Cell Lung Cancer (SCLC), relapsed ovarian 
cancer, and prostate cancer.[24] 
Satraplatin entered clinical studies in 1992. A phase II trial conducted at multiple US sites 
accrued 39 patients with HRPC. The starting dose was 120 mg/m2/day for 5 days, but most 
patients had the dose reduced to 100 mg/m2/day for 5 days because of excessive toxicity. Among 12 
patients with measurable disease, there was one partial response (PR) in a patient with liver lesions, 
six stable disease (SD), and five patients with progressive disease (PD). Among the 24 patients 
with PSA responses (defined as a > 50% decrease from the baseline value), there were two 
complete responses, eight partial responses, and 14 patients with a stable PSA level. The median 
PSA progression free survival was 33.1 weeks. Analgesic use to determine pain response was not 
performed, though only 20 patients reported analgesic use at any time during the study.  Grade 3/4 
neutropenia was reported in 52% of subjects, leukopenia in 41%, and thrombocytopenia in 54%. 
Another phase II study conducted CA142-026 was a pilot multicenter open-label phase II study 
designed to evaluate the efficacy and safety of Satraplatin plus prednisone for second-line 
treatment of patients with HRPC.  This study was again terminated as part of the decision of the 
initial commercial sponsor.  At the time of study termination, 10 subjects had been enrolled.  
Satraplatin was administered daily for 5 days every 28 days at a starting dose of 100 mg/m2/day 
and Prednisone 10 mg/day.  However, the starting dose of Satraplatin was amended to 80 mg/ 
m2/day  for 5 days every 35 days due to study drug toxicity – two out of the first four patients 
treated experienced febrile neutropenia and severe thrombocytopenia on the 100 mg/m2/day 
dose.  Therefore, the subsequent trials utilized this regimen of 35 day cycles of satraplatin at 80 
mg/ m2/day  for 5 days with prednisone 10 mg daily for 35 days.  Two phase III trials for patients 
with HRPC using daily satraplatin (35 day cycles) in combination with orally administered 


Version Date: 05-10- 2011 
18 
 
prednisone were initiated but terminated prematurely as part of a commercial decision of the 
original pharmaceutical sponsor. The first was a randomized study initiated by the EORTC in June 
1998. [33] Patients with symptomatic HRPC were randomized to treatment with satraplatin (100 
mg/m2/day for 5 days every 5 weeks) plus prednisone (10 mg bid daily) (N = 27) or prednisone alone 
(N=23). All patients have been followed until progression or death.  Forty-two patients have died, 
most due to prostate cancer. A > 50% decrease in PSA was observed in 2/23 (8.7%) on the 
prednisone alone arm versus 9/27 (33.3%) in the satraplatin + prednisone arm (P=0.046). Toxicity 
was minimal in both arms; one patient on each arm died due to stomach perforation, most likely 
related to prednisone. Compliance to treatment was excellent. The median progression-free survival 
(PFS) was twice as long in the satraplatin + prednisone arm versus the prednisone alone arm (5.2 
versus 2.6 months, p=0.023). Median overall survival (OS) also favored the satraplatin arm, 14.9 
versus 11.9 months. This difference was not statistically significant, probably due to the small patient 
numbers.  The second trial was a randomized, double blind, placebo-controlled study initiated in 
December 1998. Fourteen patients with symptomatic HRPC were enrolled and randomized to 
treatment with either 100 mg/m2/day satraplatin for 5 days plus BID administration of 10 mg 
prednisone for 5 days (N = 7), or placebo plus BID administration of 10 mg prednisone alone for 5 
days (N = 7) every 5 weeks. Additional details are in the Satraplatin Investigator Brochure.[26]  
SPARC (SatraPlatin Against Refractory Cancers) is a Phase III pivotal trial that opened in 2003.  
It is a multicenter, double-blind, placebo-controlled, randomized Phase III trial assessing 
satraplatin plus prednisone versus placebo plus prednisone as 2nd line chemotherapy treatment of 
AIPC.  Satraplatin 80 mg/m2/day or placebo was administered daily on days 1-5 of a 35-day 
cycle, and prednisone 5 mg was given twice daily on days 1-35 [34] .  A total of 950 patients 
were accrued at more than 200 clinical sites in fifteen countries on four continents.  Results from 
this study show a 40% reduction in the risk of progression, p<0.00001.  Hazard Ratio of 0.6 
(95% Confidence Interval: 0.5-0.7). The improvement seen in progression-free survival by 
patients treated with satraplatin increased over time.  Progression-free survival at the median 
(50th percentile) demonstrated a 13% improvement in patients who received satraplatin plus 
prednisone (11 weeks) compared to patients who received prednisone plus placebo (9.7 weeks).  
At 6 months, 30% of patients in the satraplatin arm had not progressed, compared to 17% of 
patients in the control arm. At 12 months, 16% of patients who received satraplatin had not 
progressed, compared to 7% of patients in the control arm.  Pain response was 24.2% for 
satraplatin and prednisone versus 13.8% for prednisone and placebo (p<0.005) and PSA response 
was 25.4% for the combination versus 12.4% for prednisone (p<0.01).  Overall survival data has 
not been reported but will be presented at the American Society of Clinical Oncology (ASCO) 
Meeting in 2007.  The treatment dosing regimen used in the SPARC trial will be followed in this 
proposed Phase II protocol. 
1.2.3 Prednisone 
Prednisone, a glucocorticoid has been shown to have significant palliative activity in patients 
with androgen-independent prostate cancer.  A previous study was done in patients with 
androgen-independent prostate cancer, that were given prednisone alone.  Patients received 10 
mg orally twice a day.  Of the 29 patients, 48% of patients had a > 25% PSA decline, 34% had a 
PSA decline > 50% and 14% experienced a PSA decline of > 75%.  The average PSA declined 
in this study population was 33%.  Average progression free survival was 2.8 months.[35]  
Prednisone has also been used with satraplatin in the previous EORTC Phase III trial as well as 
the recently concluded SPARC trial discussed in section 1.2.2. 


Version Date: 05-10- 2011 
19 
 
 
1.2.4 Background on DNA gene polymorphisms and rationale for use of satraplatin in AIPC 
Satraplatin forms the same DNA adducts as cisplatin but retains a unique carrier ligand. Platinum 
agents, with cisplatin as the prototype, have been in use for several decades and constitute the 
backbone of treatment for several malignancies.  Its main cytotoxic function has been based on 
the formation of mono- and bi-functional adducts in the DNA, which cause inter-/intrastrand 
cross linking. One mechanism by which tumors develop resistance is by increased tolerance to 
DNA damage as a result of a highly efficient DNA repair capacity.[36] Understanding of the 
multiple enzymatic pathways leading to repair of nonspecific DNA damage has been elucidated 
with the Nucleotide excision repair (NER) and Base excision repair (BER) systems. Many 
studies have indicated that polymorphic DNA repair genes influence platinum-based 
chemotherapy in a cancer-specific manner. It has been hypothesized that impaired NER/BER 
function led to decreased capacity for DNA repair of the tumors following treatment with 
cisplatin, leading to greater DNA damage, and ultimately cell death. [37-38] It also confers a 
higher risk for cancer because of the suboptimal DNA repair capability.  In particular, NER 
capability as measured by a plasmid-based host reactivation assay was significantly lower in 
prostate cancer cases.  Using cryopreserved lymphocytes collected from a clinic-based case-
control study, results showed that the mean NER capacity was significantly lower (P = 0.03) in 
140 cases (mean +/- SD, 8.06 +/- 5.17) than in 96 controls (9.64 +/- 5.49). There was a 
significant association between below-median NER capacity and prostate cancer risk: odds ratio 
(OR), 2.14; 95% confidence interval (CI), 1.19-3.86, after adjustment for age, race/ethnicity, 
smoking history, benign prostatic hyperplasia, and family history,  supporting the hypothesis that 
a deficient NER capacity  results in increased risk for prostate cancer. [39] Several key and rate-
limiting enzymes including ERCC1, XRCC1 have been studied and have increasingly been used 
to predict response to chemotherapy in several cancers such as squamous cell carcinoma of the 
head and neck,[40], Non-small cell lung cancer,[41] and ovarian cancer. [42]  .Single nucleotide 
polymorphisms (SNPs) in a given gene may affect the function of the encoded protein and 
preclinical data suggest that one polymorphism at the ERCC1 gene (C8092A) may affect its 
mRNA stability, resulting in impaired DNA repair capacity.[43] Evaluation of tumor specimens 
for expression of DNA repair genes may predict for response to platinum and ultimately, for 
survival.  In the IALT Bio study that looked at 761 tumor specimens, a benefit from cisplatin-
based adjuvant chemotherapy was associated with the absence of ERCC1 (test for interaction, 
P=0.009) [44]. This forms the basis for obtaining tumor biopsy specimens from prostate cancer 
patients in this study, especially since specific gene polymorphisms has not been extensively 
studied in prostate cancer [45]Since satraplatin DNA-adducts are efficiently repaired by 
mammalian NER pathway,[46] and less likely recognized by mismatch repair mechanism, [47] 
or post-replication repair mechanism,[48] it would be plausible that the same gene 
polymorphisms that give rise to impaired NER pathway would confer better response to 
satraplatin in patients with prostate cancer. 
1.2.5 Excision repair cross-complementation group 1 (ERCC1) 
ERCC1 forms a heterodimer with XPF and as a unit, they perform the 5’ incision which is 
specific to excision of Pt-DNA adducts.[49]  Greater levels of total ERCC1 mRNA and full 
length ERCC1 mRNA were found in ovarian cancer tissues resistant to platinum-based 
chemotherapy.[42] The most widely studied polymorphism is 19007C>T (Asn118Asn), in which 


Version Date: 05-10- 2011 
20 
 
the variant T allele was correlated to better response to platinum-based chemotherapy in 
epithelial ovarian cancer.[50] and oxaliplatin/5-FU combination chemotherapy in advanced 
colorectal cancer. [51] Another common SNP in ERCC1 is 8092C>A in 3’ UTR. It was 
suggested that this variant may affect its mRNA stability which in turn results in reduced protein 
activity.[43]  The variant A allele increased gastrointestinal toxicity in platinum treated NSCLC 
patients.[52] We have found that the ERCC1 N118N variant may occur at a lower frequency 
(around 20%) among African-Americans (unpublished data).  It is unclear how this relates to the 
higher incidence of prostate cancer that is found in African-Americans. The frequency of the 
more widely studied polymorphism ERCC1N118N wild-type is also found to occur at around 
20%, while variant alleles are about 80% (49% for the CT variant allele and 30% for the TT 
variant allele), in  control groups of Caucasian men.. (unpublished data, please see Table on 
summary of key findings on variant DNA repair genes ). Using these data, we propose that 
prostate cancer patients exhibiting ERCC1 variant alleles may have better response to a platinum 
agent such as satraplatin. 
Table on summary of key findings on variant DNA repair genes in Caucasians and African-
Americans (unpublished data) 
Single 
Nucleotide 
Polymorphism 
Genotype 
Caucasian 
African 
American 
  
 
Counts (freq.) 
Counts (freq.) 
P VALUE 
ERCC1N118N 
CC 
CT 
TT 
TOTAL 
23(0.21) 
53(0.49) 
32(0.30) 
108 
96(0.76) 
27(0.21) 
4(0.03) 
127 
<0.001 
ERCC1 C8092A 
 
CC 
AC 
AA 
TOTAL 
77(0.53) 
59(0.40) 
10(0.07) 
146 
74(0.52) 
56(0.40) 
11(0.08) 
141 
N.S 
ERCC2 K751Q 
AA 
AC 
CC 
TOTAL 
49(0.42) 
56(0.47) 
13(0.11) 
118 
81(0.56) 
57(0.40) 
6(0.04) 
144 
<0.001 
XRCC1 R399Q 
 
GG 
AG 
AA 
TOTA
L 
49(0.46) 
47(0.44) 
10(0.10) 
106 
113(0.80) 
26(0.19) 
2(0.01) 
141 
<0.001 
XRCC1 R194W 
CC 
CT 
TT 
TOTAL 
120(0.87) 
17(0.12) 
1(0.01) 
138 
133(0.90) 
14(0.09) 
1(0.01) 
148 
N.S 


Version Date: 05-10- 2011 
21 
 
Single 
Nucleotide 
Polymorphism 
Genotype 
Caucasian 
African 
American 
  
 
Counts (freq.) 
Counts (freq.) 
P VALUE 
PARP1 V762A 
TT 
CT 
CC 
TOTAL 
80(0.67) 
32(0.27) 
7(0.06) 
119 
108(0.91) 
11(0.09) 
0(0) 
119 
<0.001 (ALLELE 
FREQ.) 
1.2.6 Other DNA repair gene polymorphisms 
Xeroderma pigmentosum group D: XPD gene, also known as ERCC2, encodes for a DNA 
helicase which catalyzes another rate-limiting step in NER pathway. A sibling-based study on 
prostate cancer correlated the variant homozygotes of Asp312Asn to slightly higher risk of 
prostate cancer and the variant allele of XRCC1 Arg399Gln adds great value to this effect [53]. 
And a most recent study showed that combined genotypes with at least one variant allele in XPD 
Lys751Gln and XRCC1 Arg399Gln were strongly related to improved survival in bladder cancer 
patients treated with platinum-based chemoradiotherapy [54]. However, some discrepant results 
were found in XPD polymorphisms with relationship to platinum chemotherapy. Possessing the 
wild-type allele of Lys751Gln increased the risk of suboptimal DNA repair though the 
Asp312Asn polymorphism were not found to affect DNA repair activity [55]. The wild-type 
allele Lys751Gln was associated with better response and longer survival in colorectal cancer 
patients received 5-fluorouracil/oxaliplatin chemotherapy, and this allele was in a strong linkage 
with Asp312Asn [56]. In addition, the variant allele of Asp312Asn was related to decreased 
overall survival, especially when combined with variant allele of  XRCC1 Arg399Gln, in 
NSCLC patients treated with cisplatin/carboplatin [41]. 
Besides the NER pathways, other DNA repair proteins involved in base excision repair (BER) 
pathway, such as XRCC1 and PARP1 were also considered important because of their potential 
activities in removing platinum-DNA adducts. 
X-Ray cross complementation group 1: XRCC1 is a principle player in BER pathway. It 
stimulates endonuclease activities following the excision of a damaged base and acts as both a 
scaffold and a regulator for other BER proteins [57]. The Arg399Gln change residues were 
firstly identified by Shen et al. This  polymorphism resides in  the C-terminal side of PARP-
interacting domain [43]. The wild-type allele of Arg399Gln appeared more frequently in good 
responders to platinum-based chemotherapy in bulky cervical cancer patients [58]. Advanced 
colorectal cancer patients carrying variant allele of this substitution were more resistant to 
oxaliplatin/5-FU chemotherapy [59]. In addition, high expression levels of XRCC1 were found 
in bladder cancer patients with improved survivals following radical radiotherapy [60]. Published 
data have also shown correlations between the variant allele of Arg194Trp and increased risk of 
lung cancer [61], oral squamous cell carcinoma [62], and better response to platinum-based 
chemotherapy in advanced NSCLC [63].  
Poly (ADP-ribose) polymerase-1: PARP1 is another member of BER complex and serves in 
detecting DNA interruptions. In response to these breaks, it recruits XRCC1 and other partners 
for further processing of the damages [64]. Overexpression of XRCC1 dramatically decreased 
PARP1 activity in vivo [64]. The variant allele of Val762Ala contributed to significantly lower 
PARP1 activity and increased prostate cancer risk [65].  Furthermore, PARP1 inhibitor was 


Version Date: 05-10- 2011 
22 
 
proved to be able to increase the sensitivity of platinum compounds against platinum resistant 
ovarian tumor cells [66]. 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1 
Eligibility Criteria 
2.1.1 Inclusion Criteria 
2.1.1.1  Patients must have histopathological confirmation of prostate cancer by the Laboratory 
of Pathology of the NCI or Pathology Department of the National Naval Medical Center 
or Walter Reed Army Medical Center prior to entering this study.  Patients whose 
pathology specimens are not available may be enrolled in the trial if the patient has a 
clinical course consistent with prostate cancer and available documentation from an 
outside pathology laboratory of the diagnosis.  In cases where original tissue blocks or 
archival biopsy material is available, all efforts should be made to have the material 
forwarded to the research team for use in correlative studies. 
2.1.1.2 Patients must have metastatic progressive androgen-independent prostate cancer.  There 
must be radiographic evidence of disease (by CT scan or bone scan) after primary 
treatment that has continued to progress despite hormonal agents.  Progression requires 
that a measurable lesion is expanding, new lesions have appeared, and/or that PSA is 
continuing to rise on successive measurements. Patients must have progressive disease 
after receiving 1 prior docetaxel-based cytotoxic chemotherapy.  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.   
2.1.1.3 Patients may only have received 1 prior cytotoxic chemotherapy. For the purpose of this 
study, 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, 
administered in a similar fashion may count as a single regimen. 
2.1.1.4 Patients must have a life expectancy of more than 3 months. 
2.1.1.5 Patients must have a performance status of 0 to 2 according to the ECOG criteria. 
2.1.1.6 Patients must have adequate organ function as defined below: 
Leukocytes 
>3,000/μl 
Absolute Neutrophil Count 
>1,500/μl 
Platelets 
>100,000/μl 
Total bilirubin  
≤1.5 X  institutional upper limits of normal* 
AST(SGOT) and ALT(SGPT) 
<2.5 X institutional upper limit of normal 
creatinine 
 
OR 
Creatinine clearance 
≤1.5 X  institutional upper limits of normal  
 
>60 mL/min/1.73 m2 for patients with 
creatinine levels above institutional normal. 
*Except patients with Gilbert’s disease who may proceed despite elevated total bilirubin 
 
2.1.1.7 Patients must have recovered from any acute toxicity related to prior therapy, including 
surgery.  Toxicity should be ≤ grade 1 or returned to baseline. 


Version Date: 05-10- 2011 
23 
 
2.1.1.8 Hormonal profile:  all patients who have not undergone bilateral surgical castration must 
continue suppression of testosterone production by appropriate usage of GnRH 
agonists. 
2.1.1.9 Patients must not have any ongoing malignancies requiring active therapy.  
2.1.1.10 Patients must be able to understand and sign an informed consent form. 
2.1.1.11 Concurrent use of bisphosphonates will be allowed if patients have previously been on 
it; if patients are not on bisphosphonates at the time of study enrollment, 
bisphosphonates may be started at cycle 2. 
2.1.1.12 Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), 
but not myeloid growth factors (except after cycle 1 day 1 if clinically indicated), 
NSAIDs, and other maintenance medications prior to study entry will be allowed to 
continue their supportive therapies. 
2.1.1.13 Results from embryo-fetal development indicated that satraplatin should be considered 
a teratogen in women of childbearing potential and hazardous in respect to 
spermatogenesis for men.  For this reason, men must agree to use adequate 
contraception (abstinence; hormonal or barrier method of birth control) prior to study 
entry and for the duration of study participation.   
2.1.1.14 Patients must be able to swallow capsules 
2.1.1.15 Patients on chronic stable steroids (equivalent to no more than 10 mg of prednisone 
daily dose) used for non-cancer  treatment may be allowed on study 
2.1.2 Exclusion Criteria 
2.1.2.1 Patients who have had prior treatment with satraplatin or other platinum containing 
compounds will be excluded.  
2.1.2.2 Patients may not be receiving any other investigational agents. 
2.1.2.3 Patients with known active brain metastases are excluded from this clinical trial because 
of their poor prognosis and because they often develop progressive neurologic 
dysfunction that would confound the evaluation of neurologic and other adverse events.   
2.1.2.4 History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to satraplatin or prednisone. 
2.1.2.5  Uncontrolled intercurrent illness including, but not limited to ongoing or active serious 
infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric 
illness/social situations that would limit patient compliance with study requirements.  
2.1.2.6 Prior radiation therapy to > 30% of the bone marrow, or who have received strontium-89, 
rehenium-186, or rhenium-188 will be excluded from this trial.  Patients who have 
received prior radiotherapy must have recovered from acute toxicity due to radiation.  
Patients who have received samarium-153 are eligible for the study because samarium 
has a significantly reduced half-life compared to aforementioned isotopes.  


Version Date: 05-10- 2011 
24 
 
2.1.2.7 Patients with immune deficiency are at increased risk of lethal infections when treated 
with marrow-suppressive therapy.  Therefore, HIV-positive patients are excluded from 
the study.  
2.1.2.8 Patients with a history of major gastrointestinal surgery or pathology likely to influence 
absorption of oral medications, like bypass surgeries, Whipple’s procedure, or any 
surgery that would impair reliable absorption of oral drugs.  
2.1.2.9 Patients with a disease where corticosteroids are contraindicated, e.g. active gastric or 
duodenal ulcer, or poorly controlled insulin dependent diabetes.  Patients with well-
controlled insulin-dependent diabetes mellitus may be considered, providing they 
understand their glucose levels will increase, and their insulin dose will require 
adjusting. 
2.1.2.10 Because no dosing or adverse event data are currently available on the use of satraplatin 
in patients <18 years of age, children are excluded from this study. 
2.2 
Research Eligibility Evaluation 
2.2.1 Imaging Studies (Baseline- obtained within 4 weeks prior to enrollment):   
 Technetium-99 Bone Scintigraphy,  
 Chest X-ray,  
 CT scan of chest, abdomen and pelvis  
2.2.2 Laboratory Evaluation (Baseline- obtained within 16 days prior to enrollment) 
 Hematological Profile:  CBC with differential and platelet count, PT, aPTT, 
fibrinogen. 
 Biochemical Profile:  electrolytes, BUN, creatinine, AST, ALT, alkaline 
phosphatase, total bilirubin, calcium, phosphorus, albumin, magnesium, uric acid, 
total protein, glucose, albumin, amylase, lipase, testosterone level. 
 PSA (baseline within 7 days prior to enrollment) 
 Electrocardiogram (performed within 21 days prior to enrollment); Patients with a 
history of myocardial infarction or cardiac arrhythmias will undergo evaluation by 
cardiology. 
 
2.3 
Patient Registration 
Authorized staff must register an eligible candidate with NCI Central Registration Office (CRO) 
within 24 hours of signing consent. A registration Eligibility Checklist from the web site 
(http://intranet.cancer.gov/ccr/welcome.htm) must be completed and faxed to 301-480-0757. 
After confirmation of eligibility at Central Registration Office, CRO staff will call pharmacy to 
advise them of the acceptance of the patient on the protocol prior to the release of any 
investigational agents. Verification of Registration will be forwarded electronically via e-mail. 
Please note, it is very important for all registrars to acquire encrypted e-mail from NIH Help 
Desk, since the verification of registration includes patient’s information. A recorder is available 
during non-working hours. 
 
 


Version Date: 05-10- 2011 
25 
 
3 
Study Design 
This trial will be conducted using a single stage design. However, to protect against the unlikely 
possibility that the agent will be associated with overall progression free survival which is 
substantially below what is expected based on results from other trials, an early stopping rule 
will be implemented as follows. After 20 patients have been enrolled and 6 months have passed 
since the 20th patient has enrolled, the proportion of patients who have attained 6 months without 
progression will be determined. If this fraction is no greater than 3/20 (15% who have attained 6 
month progression free survival), then the trial will cease enrolling further patients because a 
one-sided 90% upper confidence bound on 3/20 is 30.4%, which would only indicate at best a 
modest probability of marginal consistency with what would be expected as the overall outcome 
using satraplatin.  Similarly, genotyping for ERCC1 will also be performed after the 20th patient 
to test whether we are achieving the true probability of ERCC1 wild type proportion of 20% as 
indicated in earlier studies (in Caucasians). If the true probability is as shown, the probability of 
having 0 or 1 with WT genotype is tabled: 
True WT proportion 
Probability of getting 0 or 1 with 
WT 
0.2 
7% 
0.1 
39% 
0.05 
74% 
 
Thus, if only 0 or 1 patient out of the first 20 patients should have ERCC1 WT genotype, then 
this would be more consistent with a 0.05 rather than  a 0.20 true rate of WT.  If this turns out to 
be the case, then we would re-evaluate the procedure for enrolling subjects to try to increase the 
proportion of patients with ERCC1 WT and amend the protocol accordingly. Otherwise, accrual 
to the full 66 patients will continue.  See section 9.. Statistical analysis for further review of 
statistical design.   
3.1 
Drug Administration 
3.1.1 Satraplatin administration 
Satraplatin will be administered in an outpatient basis. This is to allow for pharmacokinetic 
samples to be obtained as outlined in section 3.4.1.1.  Reported adverse events and potential risks 
are described in Section 6.  Appropriate dose modifications for satraplatin are described in 
Section 3.3.  No investigational or commercial agents or therapies other than those described 
below may be administered with the intent to treat the patient’s malignancy. 
 
Satraplatin is supplied as 1 x 5 capsules in blister strips. There are two strengths of capsules, one 
with 10 mg dose and the other with 50 mg dose.  Patient’s dose will be calculated based on body 
surface area as 80 mg/m2 dose to be given daily x 5 days, every 35-days cycle. The total dose of 
satraplatin delivered should be rounded to the nearest 10 mg dose, (i.e., if total dose is < 165 mg, 
deliver 160 mg; if total dose > or = 165 mg, deliver 170 mg) after calculation of patient BSA.  
Patients are to swallow the capsules whole with approximately 125 ml - 250 ml of any clear 
liquids. Capsules should be taken on an empty stomach (no food for 2 hours before or 1 hour 
after dosing). Satraplatin will be given as self-administered oral doses of 80 mg/m2 for days 1-5 
every 35 days. Patients will be asked to maintain a diary to document consumption of satraplatin 


Version Date: 05-10- 2011 
26 
 
as outlined in section 8 and Appendix B. 
 
Patients will be required to have weekly blood counts drawn for the first 3 cycles of the study at 
an outside laboratory or at the Clinical Center given the risk of decreased white cell count and 
platelet count from satraplatin.   
3.1.2 Prednisone administration 
Prednisone 5 mg will be administered two hours prior to satraplatin (along with antiemetic, 
outlined in section 4.2) in AM and another 5 mg of prednisone in PM, on days 1-5. On days 6-
35, patients will continue Prednisone 5 mg twice daily.  Therefore, prednisone is given 
continuously twice daily throughout the 35-day cycle. 
3.2 
Treatment Modifications 
Toxicities will be described using the Common Terminology Criteria for Adverse Events version 
3.0 (CTCAE v3).  The following adjustment will only apply if the toxicities reported are 
attributed by the investigator to be related to satraplatin and prednisone therapy. 
3.2.1 Dose modification for satraplatin: 
Dose reductions will be according to the following rules for satraplatin: 
For Grade 1 toxicity, no treatment interruption or dose reduction for either satraplatin or 
prednisone, will be made. For Grade 2 or greater toxicity, subsequent treatment with satraplatin 
will be followed as shown in the table below and following the dose reduction schema. 
 
Non-Hematologic toxicity Dose adjustments and reductions 
Grade of Non-hematologic 
toxicity (CTCAE v3.0) 
Management/dose adjustment 
Dose reduction 
Grade 1 
None 
None 
Grade 2 nausea, vomiting or 
diarrhea 
Maintain dosing with 
symptomatic treatment; 
Repeat dosing if all tablets 
appear in emesis 
None 
Persistent Grade 2 nausea, 
vomiting or diarrhea despite 
symptomatic treatment that 
remains unacceptable 
(intolerable) to the patient 
Decrease from 80mg/m2 to 
60 mg/m2** 
Decrease by 20 
mg/m2 


Version Date: 05-10- 2011 
27 
 
Non-Hematologic toxicity Dose adjustments and reductions 
Grade of Non-hematologic 
toxicity (CTCAE v3.0) 
Management/dose adjustment 
Dose reduction 
Grade 3 clinical, Grade 3 or 4 
laboratory abnormalities which 
are associated with clinical 
signs and symptoms that are 
felt to be drug-related 
Hold satraplatin and 
reevaluate the patient at least 
weekly until toxicity 
improves to ≤ Grade 1 or pre-
treatment baseline* 
Decrease by 20 
mg/m2 (i.e., if 
patient is at 
80mg/m2/day dose, 
decrease to 
60mg/m2/day)** 
Grade 4 clinical (except 
pulmonary embolism without 
significant hypoxia and 
hemodynamic instability)  
Off-study 
  
Grade 4 vomiting or diarrhea 
that can not be controlled by 
medical treatment and that 
occurs after one dose reduction  Off-study 
  
*Treatment delay should not be >8 weeks from Day 1 of prior cycle or >3 weeks from the start 
of next scheduled cycle; otherwise, patient will be taken off-treatment. 
**If patient is already at 60mg/m2, decrease further to 40mg/m2; No further dose reduction after 
40mg/m2 will be permitted 
-Non-hematologic toxicity ascribed to study drugs must resolve to baseline or ≤ grade 1, with the 
exception of alopecia; or ≤ grade 2 for pain in order for re-treatment to continue.  
3.2.2 Hematologic Toxicity: 
Given that hematologic toxicity is one of the major toxicities that may be experienced, all 
patients should have complete blood count measured and recorded weekly during the first 3 
cycles and as needed, thereafter.  However, if the ANC is ≤ 0.5 x 109/L or platelets are ≤ 25.0 x 
109/L, CBC with differential must be redrawn more frequently, at least two times per week, until 
resolved. 
 
Dose changes for satraplatin will be made based only on changes in the neutrophil and platelet 
counts.  Satraplatin will be discontinued if neutropenia (≤ 0.5 x 109/L) lasting ≥ 5 days or 
thrombocytopenia (≤ 25 x 109/L) lasting ≥ 5 days despite dose reduction to 40mg/m2/d occurs, 
or if there is retreatment delay of > 8 weeks from Day 1 of prior cycle, due to study drug-related 
hematologic toxicities. 
No growth factor support will be given prophylactically prior to starting satraplatin. 
3.2.3 Hematologic toxicity Dose adjustments and reductions 
Variable 
Finding 
Dose modification 
Platelets 
ANC 


Version Date: 05-10- 2011 
28 
 
Variable 
Finding 
Dose modification 
Platelets 
ANC 
Hematologic 
toxicity (based 
on previous 
cycle nadir*)  
≤ 25.0 x 109/L 
≤ 0.5 x 109/L 
Decrease by 20mg/m2 
dose 
Delayed 
recovery for 
Retreatment due 
to hematologic 
toxicity** 
Less than or equal to 6 weeks 
No change in dose level 
Between 6 and 8 weeks 
Decrease by 20mg/m2 
dose 
More than 8 weeks 
Off-study 
Neutropenic 
fever 
  
  
Decrease by 20mg/m2 
dose*** 
*Complete blood counts must be available on a weekly basis in the previous course 
**Time from Day 1 of prior cycle. 
 
***Growth factor support may be given for subsequent cycles as clinically indicated 
3.2.4 Retreatment guidelines: 
If satraplatin dosing is interrupted during a treatment cycle, it may be restarted as long as the 
planned 5 days of dosing occurs within an 8-day period (maximum interruption=3 days).   
If there is more than a 3 consecutive day delay, no further doses should be given in the cycle.  
The patient will be allowed to begin the next cycle a minimum of 35 days after the first day of 
the previous cycle if the criteria for re-treatment are met. 
 
Patients may be retreated every 35 days if the following criteria are met: 
-Hematologic toxicity-Absolute neutrophil count is ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L 
-Non-hematologic toxicity ascribed to study drugs must resolve to baseline or ≤ grade 1, with the 
exception of alopecia; or ≤ grade 2 for pain in order for re-treatment to continue. 
 
Laboratory tests may be performed up to 48 hours prior to the scheduled study visit and if the 
retreatment criteria are met, the patient may be retreated.  If the re-treatment criteria are not met, 
the patient may not be retreated until they are met.  If therapy has to be held for more than 8  
weeks from D1 of prior cycle, or  > 3 weeks from the scheduled treatment, then the patient will 
be taken off-treatment. 
 
With the approval of the Principal Investigator, patients may be evaluated in offices of other 
Associate Investigator’s (listed in the protocol) every other cycle starting with pre cycle 4.  Study 
medications will continue to be dispensed by the NIH pharmacy.  Restaging scans will be 
performed at NIH 
3.2.5 Dose Modification for Prednisone: 
Prednisone dose may be reduced to 5 mg once daily for ≥ grade 3 hyperglycemia or other 
toxicity attributed to prednisone.  The dose may not be re-escalated following dose reduction. 
 
Prednisone will be discontinued if untoward and unmanageable toxicity occurs (i.e., GI 
ulceration, symptomatic hyperglycemia unresponsive to medical therapy) despite dose reduction 


Version Date: 05-10- 2011 
29 
 
to 5 mg per day.  If prednisone is discontinued in the absence of disease progression, the patient 
will continue on satraplatin alone. 
4 
Correlative studies 
4.1 
Tissue analysis  
Given the nature of this pharmacologic intervention, characterization of the actual biological 
manipulation will be helpful in understanding the biological effects seen following 
administration of satraplatin.  Tissue samples may be analyzed to achieve this goal. In the 
recently published International Adjuvant Lung Cancer Trial (IALT) Bio Trial, 
immunohistochemical analysis to determine the expression of the excision repair cross-
complementation group 1 (ERCC1) protein in operative specimens of non-small-cell lung cancer 
was performed and a benefit from cisplatin-based adjuvant chemotherapy was associated with 
the absence of ERCC1 (test for interaction, P=0.009).[44] When available samples obtained from 
selected prostate cancer patients may be utilized for ERCC1 staining using a commercially 
available mouse monoclonal antibody to human ERCC1 (clone 8F1, Neomarkers). 
Pharmacokinetic analysis will provide insight into dosing efficacy as it relates to both biological 
activity and clinical response. 
 
Correlative laboratory studies for this trial will be conducted in the Clinical Pharmacology 
Section of Dr. William D. Figg at the NCI. All patients will have leukocyte collection to evaluate 
for ERCC1 expression.  Patients with accessible disease may have tumor biopsies before and 
during treatment for ERCC1 protein analysis if feasible. 
4.1.1 Accessible tumor biopsy 
Biopsies of accessible tumors will be optional, and obtained prior to initiation of therapy and 
prior to starting cycle 2 as described.   Patients should avoid the use of aspirin or non-steroidal 
anti-inflammatory drugs for 1 week prior to biopsy to ensure safety.  Accessible tumors will be 
defined as those masses which can be safely accessed by a core needle biopsy while posing 
minimal risk to the patient.  These lesions may be cutaneous or palpable or demonstrable under 
CT or ultrasound guidance.   Determination of accessibility and safety will be made jointly by an 
investigator and a staff member from Special Procedures.  Accessible tumors will be defined as 
those masses which can be safely accessed by a core needle biopsy under CT or ultrasound 
guidance or while posing minimal risk to the patient.  Gareth Peters or Kathy Compton 
(10/5A09, 301-402-3622, 102-11964) should be contacted to arrange for sample collection.  
Biopsies are optional and will be limited to those that are easily accessible and involve minimal 
risk.  The procurement of tissue samples will be discussed with patients at enrollment in the 
protocol.  Biopsies will be obtained prior to initiating Satraplatin and prednisone (0 months), and 
after cycle 1. Participation in the phase II study is in no way contingent on consent to biopsy.  If 
tissue is obtained from biopsies, the expression of ERCC1 will be assessed via 
immunohistochemical staining using commercially available antibodies.  The tissue expression 
of ERCC1 will be correlated with patient’s response to satraplatin. 
4.2 
Leukocyte analysis 
In addition to the optional direct tumor biopsy, DNA will be isolated from whole blood for 
genotyping analysis as described in section 4.3 and collection as described in 4.3.2.  
Approximately 10 mL of blood will be drawn using a 10mL EDTA tube for DNA extraction. 


Version Date: 05-10- 2011 
30 
 
The DNA will be stored at -80 C until the time of analysis. Approximately 8 mL of blood will be 
drawn using a 8mL CPT Sodium Citrate tube to isolate leukocytes to be lysed for genotyping 
analysis as described in section 4.3.2.1.  The blood will be centrifuged and the buffy coat layer of 
white blood cells will be removed, washed and pelleted by centrifugation.  The pellet will be 
frozen for future DNA extraction.  
4.3 
 Genotyping analysis:   
Genotyping will be done only on these genes and variants listed in this section: 
Polymerase-chain reaction (PCR) followed by either restriction fragment length polymorphism 
(RFLP) or direct sequencing will be used to genotype the SNPs of ERCC1 Asn118Asn (C>T, 
rs11615), 8092C>A (3’ UTR, rs3212986).  Genotyping will not be limited to ERCC1 but may 
include the following: a) XRCC1 Arg194Trp (C>T, rs1799782), Arg399Gln (G>A, rs25489), 
and b) PARP1 Val762Ala (T>C, rs1136410).   
We have excluded genotyping for XPD to avoid the possible clinical implications for carriers 
including transmission to offspring, childbearing and in the case of two mutant alleles of 
germline mutations in Xeroderma pigmentosum group D (XPD). 
4.3.1 Patient Population and Scope of Studies 
All study participants will have to provide a blood sample for genotyping of ERCC1 and other 
gene polymorphisms. The scope of the informed consent will also allow for the analysis of 
additional genes on a study specific basis. 
4.3.2 Blood sample collection  
Dr. William D Figg’s laboratory, NCI is the designated laboratory, (POC, Mr. Gareth Peters, 
10/5A09, or Ms. Kathy Compton, 301-402-3622, 102-11964). 
 
4.3.2.1 Blood collection tubes 
Prior to Day 1 of Cycle 1(may be collected at anytime during study if unavailable prior to start of 
therapy). 
 DNA - Collect blood in 9 or 10 mL polypropylene tube containing the anticoagulant 
EDTA 
- SARSTEDT Monovette® EDTA KE (9 mL), Part # 02.1333.001 or 
- Becton-Dickinson VacutainerTM K2E (10 mL), Part # 367525 or 
- Greiner Bio-One Vacuette® K3E EDTA K3 (9 mL), Part 455036 
 Blood tubes must be gently inverted several times after collection to ensure thorough 
mixing of EDTA with the sample to prevent clotting. 
 Glass tubes MUST NOT be used as they may break during transport and freeze-
thaw cycles. 
 Heparin MUST NOT be used as an anticoagulant as it may interfere with 
downstream genotyping methodology. 
 Buffy Coat - Collect blood in a 8 mL polypropylene tube containing the 
anticoagulate sodium citrate 


Version Date: 05-10- 2011 
31 
 
- Becton-Dickinson Vacutainer® CPT™ Cell Preparation Tube with Sodium 
Citrate, Part # 362761 
 Blood tubes must be gently inverted 8-10 times after collection to ensure thorough 
mixing of sodium citrate with the blood. 
 Blood tubes must be stored upright at room temperature until centrifugation. 
 
4.3.2.2 Labeling, Storage, and Tracking 
All samples sent to the Clinical Pharmacology Program (CPP) will be barcoded, with data 
entered and stored in the Patient Sample Data Management System (PSDMS) utilized by the 
CPP. This is a secure program, with access to the PSDM System limited to defined CPP 
personnel, who are issued individual user accounts. Installation of PSDMS is limited to 
computers specified by Dr. Figg. These computers all have a password restricted login screen. 
All CPP personnel with access to patient information annually complete the NIH online 
Protection of Human Subjects course.  
PSDMS creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to patients without PSDMS access. The data recorded for each sample includes the patient 
ID, name, trial name/protocol number, time drawn, cycle time point, dose, material type, as well 
as box and freezer location. Patient demographics associated with the clinical center patient 
number are provided in the system. For each sample, there are notes associated with the 
processing method (delay in sample processing, storage conditions on the ward, etc.). 
4.4 
Protocol Completion/Sample Destruction 
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20 or -80 C 
according to stability requirements.  These freezers are located onsite in the CPP and offsite at 
NCI Frederick Central Repository Services (Fisher Bioservices) in Frederick, MD. Visitors to the 
laboratory are required to be accompanied by laboratory staff at all times.  
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in the PSDM System. 
All researchers are required to sign a form stating that the samples are only to be used for 
research purposes associated with this trial (as per the IRB approved protocol) and that any 
unused samples must be returned to the CPP. It is the responsibility of the NCI Principal 
Investigator to ensure that the samples requested are being used in a manner consistent with IRB 
approval. 
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting 
the rights to use the material.  
If, at any time, a patient withdraws from the study and does not wish for their existing samples to 
be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed (or returned to the patient, if so requested), and reported as such to the 
IRB. Any samples lost (in transit or by a researcher) or destroyed due to unknown sample 
integrity (i.e. broken freezer allows for extensive sample thawing, etc.) will be reported as such 
to the IRB. 
 
 


Version Date: 05-10- 2011 
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5 
Protocol Evaluation 
5.1 
BASELINE EVALUATION 
 All patients who are deemed eligible and who sign an informed consent will be enrolled 
in this trial. 
 A complete history and physical examination, including ECOG performance status (see 
Appendix A), will be done within 16 days of enrollment.   
5.2 
Laboratory Studies (see also Appendix C – Study Calendar) 
 Serum PSA  
 CBC with differential  
 Serum chemistries (Na+, K+, Cl-, CO2, glucose, BUN, creatinine, albumin, calcium, 
magnesium, phosphorus, alkaline phosphatase, ALT, AST, total bilirubin, glucose, total 
protein, LDH) 
 -Serum testosterone level 
5.3 
IMAGING SUTIDES  
Non-invasive imaging has become a standard tool in the clinic to monitor primary and metastatic 
solid tumors.  CT scan and bone scan will be performed on all patients at study entry and after 
every 2 cycles to assess clinical response to satraplatin and prednisone. However, CT scan will 
only be obtained if baseline CT shows positive disease.   
6 
Concurrent Therapies 
Concurrent hormonal therapy with GnRH agonists to achieve testosterone suppression will be 
allowed. Concurrent anticancer treatment with chemotherapy, radiation therapy, major surgical 
procedures for prostate cancer, and nonprotocol-related immunotherapy will not be permitted. 
No growth factor support will be given prophylactically prior to starting satraplatin. 
 
Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin), NSAIDs 
and other maintenance medications prior to study entry will be allowed to continue their 
supportive therapies. Filgrastim and sargramostim or other bone marrow stimulants are permitted 
when clinically indicated only after the first cycle.  
Premedications will be used with the initiation of therapy following Clinical Center Anti-emetic 
guidelines and administered 30 – 60 minutes prior to study therapy. If granisetron is used, 
additional anti-emetics must be taken 8 hours after granisetron dose. Other anti-emetics, take as 
prescribed.  
6.1 
Nausea 
Should patients develop persistent nausea, they will be given appropriate antiemetic therapy 
following clinical center guidelines. If this agent proves ineffective, the PI may use another 
antiemetic regimen (i.e. ondansetron, tropisetron or dolasetron).  The type and period of all 
anitemetic therapy as well as any other concomitant medication administered will be recorded in 
the case report forms (CRF). 
6.2 
Diarrhea 
Patients can be given loperamide for diarrhea 


Version Date: 05-10- 2011 
33 
 
6.3 
Analgesics for pain 
Patients may use any analgesic for the treatment of pain, including narcotic and non-narcotic 
agents. 
6.4 
Concurrent use of bisphosphonates will be allowed   
7 
Criteria for Removal from protocol Therapy and Off Study Criteria 
7.1 
Criteria for Removal from Protocol Therapy 
 Clinical progression of disease, appearance of one or more new lesions and/or 
unequivocal progression of existing lesions.  
 Clear radiographic progression of disease by RECIST Criteria version 1.0 
 Grade 3 or greater toxicity attributed to treatment, as defined in section 3.3 
that does not resolve to grade 1, or pre-treatment baseline, within 3 weeks 
from next scheduled cycle. 
 Neutropenia (≤ 0.5 x 109/L) or thrombocytopenia (≤ 25 x 109/L) that occurs 
despite dose reduction to 40mg/m2/d, or if there is retreatment delay of > 8 
weeks from Day 1 of previous cycle 
 Grade 4 vomiting or diarrhea that cannot be controlled by medical treatment and 
that occurs after one dose reduction will warrant discontinuation of satraplatin. 
 Intolerable or limiting toxicity while on dose reduction of 40 mg/m2. 
 Intercurrent illness or medical circumstances. If at any time the constraints of 
this protocol are detrimental to the patient’s health, the patient may be 
removed from protocol therapy and reasons for withdrawal will be 
documented. 
 Patient requests to be taken off treatment. Reasons for withdrawal will be 
documented.  
 Noncompliance with protocol guidelines (patient removed at discretion of 
Principal Investigator). 
 General or specific changes in the patient’s condition render the patient 
unacceptable for further treatment in the judgment of the investigator.  
 Subject death. 
 Patients who meet criteria for PSA progression may continue on treatment 
unless they meet the above criteria. 
7.2 
Post Treatment Evaluation  
Once the patient is no longer receiving treatment (as per section 3.9), he may receive follow-up 
calls to monitor his well-being and progress. For patients who are taken off treatment due to 
treatment toxicities, a follow up evaluation will be conducted within a month and if subject will 
be taken off study. The phone calls will likely be annual though no specific guidelines shall be 
set.  
7.3 
Off Study Criteria: 
The patient will be considered off study upon either patient’s death or patient’s decision to no 
longer participate in the study or post treatment follow-up. 
 


Version Date: 05-10- 2011 
34 
 
7.3.1 Off-Study Procedure:  
Authorized staff must notify Central Registration Office (CRO) when a patient is taken off-
study. An off-study form from the web site (http://intranet.cancer.gov/ccr/welcome.htm) main 
page must be completed and faxed to 301-480-0757. 
8 
Data Collection 
8.1 
Patient Records and Quality Assurance 
Data will be collected according to GCP (Good Clinical Practice Guidelines). Complete medical 
records on each patient treated on the protocol, including primary documentation (e.g., 
laboratory reports, x-ray reports, scan reports, pathology reports, physician notes, etc.) will be 
maintained and confirm the following: 
 The patient met each eligibility criterion. 
 Signed informed consent was obtained prior to treatment. (An on-study confirmation of 
eligibility form will be filled out before entering the study.) 
 Documentation of specific dates and times of all treatments, doses administered, and the 
reason for any dose modification.  
 Toxicity was assessed according to protocol (see section 11). 
 Response was assessed according to protocol (x-ray, scan, lab reports, dated notes on 
measurements, and clinical assessment, as appropriate). 
Data will be entered in a secure electronic database, NCI C3D database. Completed eligibility 
checklists (developed by Central Registration Office, CRO), and blood sample flow sheets will 
also be stored. Copies of all expedited reports submitted to the IRB and IND Safety Reports will 
be kept in the regulatory binder. Complete records must be maintained on each patient, including 
the medical record with any supplementary information obtained from outside laboratories, 
radiology reports, or physician's records. These records will serve as the primary source material.  
8.1.1 Drug Accountability  
The unused satraplatin blister packs will be returned for drug accountability at each clinic visit.  
An oral study agent case report form will be used to document drug accountability for each 
patient on this study.  Unused agent, which is not returned to the patient for the next dose cycle, 
will be disposed of according to the Procedure of Disposal of Returned Oral agents. The 
Investigator, or a responsible party designated by the investigator, must maintain a careful record 
of the inventory and disposition of all agents received from DCTD using the NCI Drug 
Accountability Record Form.  See the CCR Standard Operating Procedure: Conducting and 
Documenting Drug Accountability for Oral Investigational Agents that are Self Administered by 
Patients  (http://ccrintra.cancer.gov/clin_ops/policies/SOPCLIN1.pdf).Patients will use a diary to 
document daily drug intake and adverse events. (See Appendix B) 
8.2 
Evaluation of Disease 
For the purposes of this study, patients should be re-evaluated for response every 2 cycles for the 
duration of the study.   


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35 
 
8.2.1 Definitions 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) Committee[67].  
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are 
used in the RECIST criteria. Note:  Lesions are either measurable or non-measurable using the 
criteria provided below. The term “evaluable” in reference to measurability will not be used 
because it does not provide additional meaning or accuracy. 
 
8.2.1.1 Measurable disease 
Measurable lesions are defined as those that can be accurately measured in at least one 
dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, 
x-ray) or as >10 mm with spiral CT scan.  All tumor measurements must be recorded in 
millimeters (or decimal fractions of centimeters). 
8.2.1.2 Non-measurable disease 
All other lesions (or sites of disease), including small lesions (longest diameter <20 mm with 
conventional techniques or <10 mm using spiral CT scan), are considered non-measurable 
disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses (not followed by 
CT or MRI), and cystic lesions are all non-measurable. 
8.2.1.3 Target lesions 
All measurable lesions up to a maximum of five lesions per organ and 10 lesions in total, 
representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline.  Target lesions should be selected on the basis of their size (lesions with 
the longest diameter) and their suitability for accurate repeated measurements (either by imaging 
techniques or clinically).  A sum of the longest diameter (LD) for all target lesions will be 
calculated and reported as the baseline sum LD.  The baseline sum LD will be used as reference 
by which to characterize the objective tumor response. 
8.2.1.4 Non-target lesions 
All other lesions (or sites of disease) should be identified as non-target lesions and should also 
be recorded at baseline.  Non-target lesions include measurable lesions that exceed the maximum 
numbers per organ or total of all involved organs as well as non-measurable lesions.  
Measurements of these lesions are not required, but the presence or absence of each should be 
noted throughout follow-up.  
8.2.2 Guidelines for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment. 
Note: Tumor lesions that are situated in a previously irradiated area might or might not be 
considered measurable. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination when both methods have been used to assess the 


Version Date: 05-10- 2011 
36 
 
antitumor effect of a treatment. 
Clinical lesions.  Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes).  In the case of skin lesions, documentation by 
color photography, including a ruler to estimate the size of the lesion, is recommended.  
Chest x-ray.  Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung.  However, CT is preferable.  
Conventional CT and MRI.  These techniques should be performed with cuts of 10 mm or less 
in slice thickness contiguously.  Spiral CT should be performed using a 5 mm contiguous 
reconstruction algorithm.  This applies to tumors of the chest, abdomen, and pelvis.  Head and 
neck tumors and those of extremities usually require specific protocols. 
Ultrasound (US).  When the primary endpoint of the study is objective response evaluation, US 
should not be used to measure tumor lesions.  It is, however, a possible alternative to clinical 
measurements of superficial palpable lymph nodes, subcutaneous lesions, and thyroid nodules.  
US might also be useful to confirm the complete disappearance of superficial lesions usually 
assessed by clinical examination. 
Endoscopy, Laparoscopy.  The utilization of these techniques for objective tumor evaluation 
has not yet been fully and widely validated.  Their uses in this specific context require 
sophisticated equipment and a high level of expertise that may only be available in some centers.  
Therefore, the utilization of such techniques for objective tumor response should be restricted to 
validation purposes in reference centers. However, such techniques may be useful to confirm 
complete pathological response when biopsies are obtained. 
Cytology, Histology.  These techniques can be used to differentiate between partial responses 
(PR) and complete responses (CR) in rare cases (e.g., residual lesions in tumor types, such as 
germ cell tumors, where known residual benign tumors can remain). 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or stable disease is 
mandatory to differentiate between response or stable disease (an effusion may be a side effect of 
the treatment) and progressive disease. 
8.3 
Response Criteria 
8.3.1 Evaluation of target lesions 
 
Complete Response (CR):Disappearance of all target lesions 
 
Partial Response (PR): 
 
At least a 30% decrease in the sum of the 
longest diameter (LD) of target lesions, taking 
as reference the baseline sum LD 
 
Progressive Disease (PD): 
At least a 20% increase in the sum of the 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 
 
Stable Disease (SD):  
 
Neither sufficient shrinkage to qualify for PR 
nor sufficient increase to qualify for PD, taking 
as reference the smallest sum LD since the 


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treatment started 
 
8.3.2 Evaluation of non-target lesions 
 
Complete Response (CR): 
Disappearance of all non-target lesions and 
normalization of tumor marker level 
 
Incomplete Response/ 
Stable Disease (SD):  
Persistence of one or more non-target lesion(s) 
and/or maintenance of tumor marker level above 
the normal limits 
 
Progressive Disease (PD): 
Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target 
lesions 
 
Although a clear progression of “non-target” lesions only is exceptional, in such circumstances 
the opinion of the treating physician should prevail, and the progression status should be 
confirmed at a later time by the review panel (or study chair). 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for a 
patient to be considered in complete clinical response. 
8.3.3 Evaluation of best overall response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria (see section 11). 
 
 
Target Lesions 
 
Non-Target Lesions 
 
New Lesions 
 
Overall Response 
 
CR 
 
CR 
 
No 
 
CR 
 
CR 
 
Incomplete 
response/SD 
 
No 
 
PR 
 
PR 
 
Non-PD 
 
No 
 
PR 
 
SD 
 
Non-PD 
 
No 
 
SD 
 
PD 
 
Any 
 
Yes or No 
 
PD 
 
Any 
 
PD 
 
Yes or No 
 
PD 


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Target Lesions 
 
Non-Target Lesions 
 
New Lesions 
 
Overall Response 
 
Any 
 
Any 
 
Yes 
 
PD 
 
Note: 
 
 Patients with a global deterioration of health status requiring discontinuation 
of treatment without objective evidence of disease progression at that time 
should be classified as having “symptomatic deterioration.”  Every effort 
should be made to document the objective progression, even after 
discontinuation of treatment. 
 
 In some circumstances, it may be difficult to distinguish residual disease from 
normal tissue.  When the evaluation of complete response depends on this 
determination, it is recommended that the residual lesion be investigated (fine 
needle aspirate/biopsy) before confirming the complete response status. 
8.3.4 Confirmatory Measurement/Duration of Response 
8.3.4.1 Duration of overall response 
The duration of overall response is measured from the time measurement criteria are met for CR 
or PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented. 
8.3.4.2 Duration of Stable Disease 
Stable disease is measured from the start of the treatment until the criteria for progression are 
met, taking as reference the smallest measurements recorded since the treatment started.  
8.3.5 Biochemical Response Criteria –PSA measurements (PSA Consensus Criteria) [68] 
8.3.5.1 PSA Decline of ≥50% 
 A decline of PSA of at least 50% (confirmed by a second value at least 4 weeks after the first) 
with no other evidence of disease progression. 
8.3.5.2 PSA Progression (all progression dates require to be confirmed by a second value after 
the first no sooner than 4 weeks after the initial measurement) 
A 50% increase in PSA over nadir (confirmed by a second reading four weeks later) in patients 
whose PSA has fallen by at least 50%. PSA increase must be at least 5ng/ml. 


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8.3.5.3 A 25% increase in PSA over nadir (confirmed by a second reading) in patients whose 
PSA has not fallen by at least 50%.  PSA increase must be at least 5ng/ml. 
8.3.5.4 A 25% increase in PSA over baseline in patients whose PSA has not decreased.  PSA 
increase must be at least 5ng/ml. 
8.3.5.5 Time to PSA Progression 
The time between the first day of treatment to the day of PSA progression as described in 8.2.5.2 
the day of progression is defined as the first study day when the PSA level meets progression 
criteria (not the day of verification). 
8.3.5.6 Patients may continue to receive satraplatin as long as they do not have clear evidence of 
radiographic or clinical progression.  
8.4 
Toxicity Criteria 
This study will utilize the CTCAE version 3.0 for grading adverse events. A copy of the CTCAE 
version 3.0 is available at http://ctep.cancer.gov. All appropriate treatment areas will have access 
to a copy of the CTCAE version 3.0.  
9 
Statistical Analysis 
The primary objective of this single arm study is to determine if the presence of a polymorphism 
which is associated with DNA damage repair may be associated with an impact on the 
progression free survival of patients with metastatic prostate cancer. 
A total of 66 evaluable patients will be accrued to the study and the evaluation will take place 
based upon the following anticipated characteristics of the trial: 
The particular polymorphism of interest, ERCC1, has a WT (CC) prevalence of 19% in 
Caucasians (n=108) and 77% in African Americans (n=127). (Unpublished data) Based upon an 
estimate that 15% of projected patients to be enrolled on the study will be African American, the 
overall percentage of patients expected to have the WT genotype is 28%, and thus 72% are 
expected to express other genotypes other than wild type (TT or CT). Other studies have 
suggested that the presence of the WT genotype is associated with potentially lower progression 
free survival probabilities and that having the other genotypes would convey a more favorable 
prognosis [69]. 
This trial will treat all enrolled patients with satraplatin 80 mg/m2 dose on days 1-5 of every 35-
day cycle plus Prednisone 5 mg twice daily every 35 days, based on the Phase III SPARC trial. 
Preliminary data from this trial with a similar population of prostate cancer patients treated with 
the same agent had a 39% 6 month progression-free survival when pain is not included in the 
determination of PFS. It is unknown whether the results in this trial will be the same, but it will 
be conservatively estimated that for all patients taken together, the 6 month progression free 
survival will be the same 39%. If the patients enrolled on the present trial are distributed in the 
approximately expected proportion of 72% with non-wild type genotypes and 28% wild type, it 
would be of interest to determine if a modest difference in the proportion of patients who have 
not progressed by 6 months can be detected on the basis of their genotype. As this is meant to be 
a pilot investigation, using a one-tailed 0.10 alpha level Fisher’s exact test, with 20 patients 
enrolled who have the wild type and 46 who have other genotypes (approximately a 28:72 split), 
would provide 80% power to detect a difference between proportions of patients without 


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progression at 6 months of 20% vs. 50%.  
Although the primary endpoint will be determined using a Fisher’s exact test, Kaplan-Meier 
curves with a log-rank evaluation will also be performed, although this will be considered a 
secondary analysis. 
The entire group of 66 patients will also be evaluated using a Kaplan-Meier curve to describe the 
progression free survival of the group as a whole, as a secondary evaluation as well.  
Overall survival will also be determined to the extent possible for the group of 66 patients as a 
whole and also as a function of the genotype expression described; this will be considered a 
secondary evaluation. 
The trial will be conducted using a single stage design. However, to protect against the unlikely 
possibility that the agent will be associated with overall progression free survival which is 
substantially below what is expected based on results from other trials, an early stopping rule 
will be implemented as follows. After 20 patients have been enrolled and 6 months have passed 
since the 20th patient has enrolled, the proportion of patients who have attained 6 months without 
progression will be determined. If this fraction is no greater than 3/20 (15% who have attained 6 
month progression free survival), then the trial will cease enrolling further patients because a 
one-sided 90% upper confidence bound on 3/20 is 30.4%, which would only indicate at best a 
modest probability of marginal consistency with what would be expected as the overall outcome 
using this agent.  We will also perform genotyping for ERCC1 after the 20th patient, this is to test 
whether we are achieving the true probability of ERCC1 wild type proportion of 20% as 
indicated in earlier studies (in Caucasians). If the true probability is as shown, the probability of 
having 0 or 1 subject with WT genotype is tabled: 
True WT proportion 
Probability of getting 0 or 1 with 
WT 
0.2 
7% 
0.1 
39% 
0.05 
74% 
 
Thus, if only 0 or 1 patient out of the first 20 patients should have ERCC1 WT genotype, then 
this would be more consistent with  a 0.05 rather than  a 0.20 true rate of WT.  If this turns out to 
be the case, then we would re-evaluate the procedure for enrolling subjects to try to increase the 
proportion of patients with ERCC1 WT and amend the protocol accordingly. 
Toxicity of the agent will also be tabulated for all patients taken as a group, and potentially by 
type of polymorphism genotype expression in the event that this may have some association. The 
distributions of toxicity identified will be compared informally to data from the same agent in 
other trials. 
This trial will also explore other biologic correlates, as outlined above using genotyping for other 
DNA repair gene polymorphisms, white blood cell collections, and tumor biopsy, whenever 
possible.  Monthly PSA, CBC, and serum chemistries will be performed at baseline and monthly 
thereafter, with CT scans and bone scans to be performed at baseline and every 10 weeks of 
treatment until progression. The comparisons will be made without any correction for multiple 
comparisons because of the exploratory and secondary nature of the evaluations. 


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9.1 
Sample Size/Accrual Rate 
Based on previous efforts in recruiting patients with this disease onto trials at the NCI, it is 
anticipated that 30 patients per year may be able to enroll onto this protocol. Thus, it is expected 
that accrual to this trial can be completed in approximately 2.5 years if all 66 patients are to be 
enrolled. 
9.2 
Stratification Factors 
There are no stratification factors 
9.3 
Analysis of Secondary Endpoints 
Genotyping, PSA, and molecular endpoints will be evaluated on the protocol in all available 
enrolled patients.  These will all be considered exploratory analyses, and will not have their 
statistical results adjusted for multiple comparisons. However, all interesting findings will be 
carefully interpreted as hypothesis generating. 
10 HUMAN SUBJECTS PROTECTIONS 
10.1 Rationale for subject selection 
Subjects treated on this study, will be individuals with metastatic prostate cancer, which has 
recurred (or persisted) after appropriate standard treatment.  Individuals of any race or ethnic 
group will be eligible for this study.  Eligibility assessment will be based solely on the patient’s 
medical status.  Recruitment of patients onto this study, will be through standard CCR 
mechanisms.  No special recruitment efforts will be conducted. 
10.2 Participation of Children 
Individuals under the age of 18 will not be eligible to participate in this study because they are 
unlikely to have prostate cancer, and because of unknown toxicities in pediatric patient. 
10.3 Evaluation of benefits and risks/discomforts 
The potential benefit to a patient that goes onto study, is a reduction in the bulk of their tumor 
and improvement in their bony lesions, which may or may not have favorable impact on 
symptoms and/or survival.  Potential risks include the possible occurrence of any of a range of 
side effects that are listed in the Consent Document.  The procedure for protecting against or 
minimizing risks will be to medically evaluate patients on a regular basis. 
10.4 Risks to patients in relation to anticipated benefits 
For patients with androgen-independent prostate cancer, median survival is in the range of 12-18 
months.  Potential risks include the possible occurrence of any of a range of side effects listed in 
section 8.  
Risk of serial biopsies: All care will be taken to minimize risks that may be incurred by tumor 
sampling.  However, there are procedure-related risks (such as bleeding, infection and visceral 
injury) that will be explained fully during informed consent. If patients suffer any physical injury 
as a result of the biopsies, immediate medical treatment is available at the NIH’s Clinical Center 
in Bethesda, Maryland.  Although no compensation is available, any injury will be fully 
evaluated and treated in keeping with the benefits or care to which patients are entitled under 
applicable regulations. 


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10.5 Consent process 
Patients will meet with an associate or principal investigator on the trial in the Prostate Cancer 
Clinic, during the initial evaluation for this study.  During that meeting, the investigator will 
inform patients of the purpose, alternatives, treatment plan, research objectives and follow-up of 
this trial.  The investigator will then provide a copy of the IRB-approved informed consent 
document that is included in this protocol.  The patient will be allowed to take as much time as 
he wishes, in deciding whether or not he wishes to participate.  If a prolonged period of time 
expires during the decision making process (several weeks, as an example), it may be necessary 
to reassess the patient for protocol eligibility.  The original signed consent goes to Medical 
Records; copy placed in research record. 
All patients must have a signed informed consent form and an on-study (confirmation of 
eligibility) form filled out and signed by a participating investigator before entering on the study. 
11 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN 
11.1 DEFINITIONS 
11.1.1 Adverse Event 
An adverse event is defined as any reaction, side effect, or untoward event that occurs during the 
course of the clinical trial associated with the use of a drug in humans, whether or not the event 
is considered related to the treatment or clinically significant. For this study, AEs will include 
events reported by the patient, as well as clinically significant abnormal findings on physical 
examination or laboratory evaluation. A new illness, symptom, sign or clinically significant 
laboratory abnormality or worsening of a pre-existing condition or abnormality is considered an 
AE.  All AEs must be recorded on the AE case report form unless otherwise noted below. 
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed until satisfactory resolution. AEs should be reported up to 30 days 
following the last dose of study drug.  AEs that are considered treatment related, expected, 
continuing, but not resolvable by 30 days after treatment completion (e.g., alopecia) will not be 
followed after the 30-day period.  
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following: 
• 
Results in discontinuation from the study 
• 
Is associated with clinical signs or symptoms  
• 
Requires treatment or any other therapeutic intervention 
• 
Is associated with death or another serious adverse event, including hospitalization.  
• 
Is judged by the Investigator to be of significant clinical impact 
• 
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 


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Lymphopenia, alkaline phosphatase and lactate dehydrogenase of any grade will not be captured 
as Adverse Events. 
11.1.2 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. 
11.1.3 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in 
the investigator brochure or is not listed at the specificity or severity that has been observed; or, 
if an investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. 
"Unexpected”, also refers to adverse events or suspected adverse reactions that are mentioned in 
the investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
11.1.4 Serious  
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
 
Death, 
 
A life-threatening adverse drug experience 
 
Inpatient hospitalization or prolongation of existing hospitalization 
 
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 A congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
11.1.5 Disability 
A substantial disruption of a person’s ability to conduct normal life functions. 
11.1.6 Life-threatening adverse drug experience 
Any adverse event or suspected adverse reaction that places the patient or subject, in the view of 
the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused death. 
11.1.7 Protocol Deviation (NIH definition) 
A protocol deviation is any change, divergence, or departure from the study design or procedures 
of a research protocol that is under the investigator’s control and that has not been approved by 
the IRB.  


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11.1.8 Protocol Violation (NIH definition) 
Any change, divergence, or departure from the study procedures in an IRB-approved research 
protocol that has a major impact on the subject’s rights, safety, or well-being and/or the 
completeness, accuracy or reliability of the study data. 
11.1.9 Unanticipated Problem 
Any incident, experience, or outcome that: 
• 
 Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
• 
Is related or possibly related to participation in the research; AND 
• 
Places subjects or others at a greater risk of harm (including physical, psychological, 
economic, or social harm) than was previously known or recognized. 
11.2 NCI-IRB REPORTING 
11.2.1 NCI-IRB Expedited Reporting of Adverse Events, Unanticipated Problems, and Deaths 
The Protocol PI will report to the NCI-IRB: 
• 
All unexpected serious adverse events that are possibly, probably, or definitely related to 
the research  
• 
All deaths, except deaths due to progressive disease  
• 
All Protocol Violations or Deviations 
• 
All Unanticipated Problems 
Reports must be received by the NCI-IRB within 7 working days of PI awareness via iRIS. 
11.2.2 NCI-IRB Requirements for PI Reporting of Adverse Events at Continuing Review 
The protocol PI will report to the NCI-IRB:  
1. 
All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research;  
2. 
All Grade 3 and 4 events that are possibly, probably or definitely related to the research;  
3. 
All Grade 5 events regardless of attribution;  
4. 
All Serious Events regardless of attribution.  
NOTE: Grade 1 events are not required to be reported.  
11.2.3 NCI-IRB Reporting of IND Safety Reports 
Only IND Safety Reports that require a sponsor recommended change to the protocol or the 
consent form or in the opinion of the PI increases risks to study participants will need to be 
reported to the NCI IRB. 


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11.3 NCI GUIDANCE FOR REPORTING EXPEDITED ADVERSE EVENTS FOR 
MULTI-CENTER TRIALS 
The site PI must immediately report to the coordinating center PI any serious adverse event, 
whether or not considered drug related, including those listed in the protocol or investigator 
brochure and must include an assessment of whether there is a reasonable possibility that the 
drug caused the event within 48 hours of PI awareness of the event.  The Site PI must also report 
any protocol deviations or violations to the coordinating center PI within 7 days of PI awareness. 
Participating centers must also submit the report to their IRB in accordance with their 
institutional policies.  
11.4 IND SPONSOR REPORTING CRITERIA  
An investigator must immediately report to the sponsor any serious adverse event, whether or not 
considered drug related, including those listed in the protocol or investigator brochure and must 
include an assessment of whether there is a reasonable possibility that the drug caused the event.  
Study endpoints that are serious adverse events (e.g. all-cause mortality) must be reported in 
accordance with the protocol unless there is evidence suggesting a causal relationship between 
the drug and the event (e.g. death from anaphylaxis).  In that case, the investigator must 
immediately report the death to the sponsor. 
11.5 FDA REPORTING CRITERIA 
11.5.1 Safety Reports to the FDA (Refer to 21 CFR 312.32) 
The Sponsor will notify FDA  via phone, fax, or email of any unexpected fatal or life-threatening 
suspected adverse reactions as soon as possible but no later than 7 calendar days of initial receipt 
of the information. This will be followed with a written report within 15 days using the 
MedWatch Form 3500a.  
The study Sponsor will notify FDA in writing of any suspected adverse reaction that is both 
serious and unexpected as soon as possible but no later than 15 calendar days after initial receipt 
of the information using the MedWatch Form 3500a. If FDA requests any additional data or 
information, the sponsor must submit it to the FDA as soon as possible, but no later than 15 
calendars days after receiving the request.  
The study Sponsor will also report expeditiously as above: 
• 
any findings from clinical, epidemiological, or pooled analysis of multiple studies or any 
findings from animal or in vitro testing that suggest a significant risk in humans exposed 
to the drug 
• 
clinical important increase in the rate of a serious suspected adverse reaction over that 
listed in the protocol or investigator brochure.  
11.5.2 FDA Annual Reports (Refer to 21 CFR 312.33) 
The study Sponsor will submit a brief report annually of the progress of the trial within 60 days 
of the anniversary date that the IND went into effect as indicated in 21CFR 312.33, and any 
associated FDA correspondences regarding the IND annual report.  
11.5.3 Expedited Adverse Event Reporting Criteria to the IND Manufacturer 
The initial telephone/facsimile report should contain as much information as is available 


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concerning the event in order to permit Agennix Inc. to file a report, which satisfies regulatory 
requirements. Initial telephone report of SAE must be followed-up by a completed SAE report 
(signed by the investigator) faxed to the Clinical Operations office of Agennix Inc. or designee. 
The event should also be entered into the source documents and case report forms, as 
appropriate.  
If only limited information is initially available, follow-up reports will be required. A completed 
SAE form report should follow the initial phone call or incomplete fax report within 5 working 
days for all SAEs.  
When additional information is available, a follow-up SAE report form should be faxed to the 
Agennix, Inc, or designee.  
Any adverse events that are initially ‘non-serious’ but become ‘serious’ shall be reportable 
according to the time of the most recent classification. 
One serious adverse event report (SAER) form will be completed per serious adverse event 
(SAE).  The SAE term should match with the term captured on the AE page of the CRF.  In 
order to avoid vague, ambiguous, or colloquial expressions, the AE term should be recorded in 
standard medical terminology. 
For all serious adverse events, the Principal Investigator or an Associate Investigator will be 
responsible for completing the SAE Report Form and will fax the SAE Form within 24 hours of 
their knowledge of the event to Agennix Inc.  
Noshin Ahmed, MD 
Clinical Program Manager 
Clinical Operations 
Agennix Incorporated 
101 College Road East 
Princeton, New Jersey  08540 USA 
Tel.: +1 609 524 1052 
Fax: +1 609 524 1086 
Email: drugsafety@gpc-biotech.com 
 
11.6 DATA AND SAFETY MONITORING PLAN 
11.6.1 Principal Investigator/Research Team  
The clinical research team will meet weekly when patients are being actively treated on the trial 
to discuss each patient. Decisions about dose level enrollment and dose escalation if applicable 
will be made based on the toxicity data from prior patients.  
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Adverse events will be reported as required above. Any safety concerns, 
new information that might affect either the ethical and or scientific conduct of the trial, or 
protocol deviations and violations will be immediately reported to the IRB using iRIS and if 
applicable to the Sponsor.  
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 


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research staff.  
11.6.2 Sponsor Monitoring Plan 
This trial will be monitored by personnel employed by Harris Technical Services on contract to 
the NCI, NIH. Monitors are qualified by training and experience to monitor the progress of 
clinical trials. Personnel monitoring this study will not be affiliated in any way with the trial 
conduct. 
At least 25% of enrolled patients’ will be randomly selected and monitored at least quarterly, 
base on accrual rate. The patients selected will have 100% source document verification done. 
Additional monitoring activities will include: adherence to protocol specified study eligibility, 
treatment plans, data collection for safety and efficacy, reporting and time frames of adverse 
events to the NCI IRB and FDA, and informed consent requirements. Written reports will be 
generated in response to the monitoring activities and submitted to the Principal investigator and 
Clinical Director or Deputy Clinical Director, CCR, NCI. 
11.6.3 Safety Monitoring Committee (SMC) 
This protocol will require oversight from the Safety Monitoring Committee (SMC).  Initial 
review will occur as soon as possible after the annual NCI-IRB continuing review date.   
Subsequently, each protocol will be reviewed as close to annually as the quarterly meeting 
schedule permits or more frequently as may be required by the SMC.   For initial and subsequent 
reviews, protocols will not be reviewed if there is no accrual within the review period. Written 
outcome letters will be generated in response to the monitoring activities and submitted to the 
Principal investigator and Clinical Director or Deputy Clinical Director, CCR, NCI. 
12 Collaborative Agreement  
The agent Satraplatin, supplied by Aggenix, Inc. used in this protocol is provided to the NCI 
under a Collaborative Agreement (CTA) between the Pharmaceutical Company and the Center 
for Cancer Research. 
13 PHARMACEUTICAL INFORMATION 
13.1 Satraplatin (IND 101,655)   
13.1.1 Source:   
Satraplatin, an investigational agent, will be supplied by Agennix Incorporated, Inc 
13.1.2 Chemical name and identification 
Chemical Name: bis(acetato)amine dichloro cyclohexylamine platinum (IV), is a member of 
a novel class of platinum (IV) compounds   
Other Names:  
JM-216 
Classification:  
Platinum analogue; platinum (IV) compounds   
Mechanism of Action: 
Like other platinum agents, satraplatin exerts its biological 
activity via reactive biotransformation products that bind to DNA causing the inhibition 
of DNA replication , cell cycle arrest, and induction of apoptosis. Satraplatin is absorbed 
when administered by the oral route. The lipophilic properties of these compounds, and 
hence their absorption, are largely determined by the nature of the axial acetate ligands. 
Unlike the square planar platinum (II) complexes, cisplatin and carboplatin, Satraplatin is an 
octahedral platinum (IV) compound. 


Version Date: 05-10- 2011 
48 
 
Molecular Formula: C10H22N2Cl2O4Pt 
 
M.W.: Satraplatin molecular weight is 500.29.  
13.1.3 How Supplied:   
Satraplatin capsules are either packaged in a) thermoformed blister packages constructed of  a 
highly moisture impermeable and light protective film (dark amber ACLAR) and a push-through 
aluminum foil backing or b) in a primary package of aluminum blister strips and a push-through 
aluminum foil backing .Satraplatin is supplied as 1x5 capsules in blister strips. There are two 
strengths of capsules, one with 10 mg dose and the other with 50 mg dose.  
13.1.4 Storage:  
 
 
Store at controlled room temperature (15ºC -30ºC) and should be protected from light. Studies 
carried out in the presence of high humidity showed no apparent degradation of study drug. 
13.1.5 Stability:  
 
 
The drug product (10 and 50 mg satraplatin capsules) is labeled for storage at room temp. (15-30 
°C) when contained within the secondary packaging (carton, box etc.).  When stored under these 
conditions, stability is good to at least 30 months.  All clinical supplies are on a formal stability 
or reassay program.  Use-dating is monitored closely and extended annually. 
13.1.6 Route of Administration:  
Oral.   
13.1.7 Reported Adverse Events and Potential Risks:   
Body as a whole:  
fatigue or asthenia, chills, headache, pain in chest or 
back, arthralgia, extremity pain, sweating, myalgia, 
bone pain 
Hematologic: 
myelosuppression, more specifically neutropenia and 
thrombocytopenia 
Lung: 
cough increased, dyspnea 
Gastrointestinal:  
diarrhea, nausea, vomiting, stomatitis, dyspepsia, 
anorexia, constipation, elevated liver enzymes, 
abdominal 
pain/cramping, 
nausea, 
flatulence, 
dyspepsia 
Hepatic: 
increased bilirubin, ALT, AST, and alkaline 
phosphatase 
Metabolic and Nutritional: decreased weight 
Renal: 
nephrotoxicity 
Neurologic: 
neurotoxicity(paresthesia), 
ototoxicity(deafness,otalgia, disorder or tinnitus), 
dizziness, changes in taste preservation 
Musculoskeletal: 
arthralgia 
Cardiovascular:  
tachycardia,syncope, hypotension 
Other: 
voice changes, hemoptysis 


Version Date: 05-10- 2011 
49 
 
13.1.8 Method of Administration:  Satraplatin should be taken with at least 120 ml to 240 mL 
of clear liquids (4-8 fluid ounces) and should be given without food (no food for 2 hours 
before or 1 hour after dosing).  
13.1.9 Potential Drug Interactions 
 
 
Satraplatin, has been shown to non-specifically inhibit numerous CYP450 isoenzymes in vitro.  
The clinical significance of the inhibition of CYP450 enzymes by satraplatin is unknown. Based 
on these in vitro data, close monitoring is recommended for patients taking agents with narrow 
therapeutic indices and metabolized by the liver, such as warfarin, phenytoin, quinidine, 
carbamazepine, phenobarbital, cyclosporine, and digoxin, and that patients should be monitored 
closely for drug interactions or adverse reactions to concomitant medications.  Investigators are 
cautioned to adjust concomitant medication dosages as appropriate.   
13.1.10Availability 
Satraplatin is manufactured/supplied by Agennix Incorporated. 
13.1.11 Agent Accountability 
The investigator, or a responsible party designated by the investigator, must maintain a careful 
record of the inventory and disposition of all drugs received from Agennix Incorporated using 
the NCI Drug Accountability Record Form (DARF).   Satraplatin, as an oral self-administered 
investigational agent, will be properly accounted for, handled, and disposed in accordance with 
CCR Policy # Clin-1 “Policy on Documenting, Handling and Disposing of Oral Investigational 
Agents that are Self-Administered by NCI CCR patients.”  The Standard Operating Procedure # 
Clin-1 “Standard Operating Procedure for Conducting and Documenting Drug Accountability for 
Oral Investigational Agents that are Self Administered by Patients at the CCR” identifies all 
activities associated with drug accountability for orally self administered investigational agents.  
Patients will be instructed to document on a study diary the daily intake of satraplatin and 
prednisone, including the time the dose is taken, and whether or not any doses are missed 
(Appendix B).  They will bring the study diary and any unused drug to their clinic appointments.  
Clinic staff will (1) collect all “old” [i.e., empty bottle(s), partial bottle(s) or full bottle(s)] of 
study drug; (2) perform a capsule count and record the results on the approved CCR Pill Count 
Case Report Form which is to be maintained in the research record; (3) dispense the partial and 
full bottle(s) of satraplatin to the patient.  Unused study drug is to be returned to the research 
nurse who will dispose of it according to the SOP. 
Upon completion or termination of the study, all unused and/or partially used study drug must be 
returned to Agennix Incorporated., if not authorized to be destroyed at the site. All drug returns to 
Agennix Incorporated must be accompanied by the appropriate documentation and be clearly 
identified by protocol number and study site number on the outermost shipping container. 
The study subject should return all unused and/or partially used study drug at the end of each dosing 
cycle. Study drug to be returned includes study drug returned by subjects unused and/or partially 
used as well as drug wasted (e.g., dropped, incorrect dose, drug dispensed but not given). If drug may 
be destroyed at the site, it is the Investigator's responsibility to ensure that arrangements have been 
made for the disposal, written authorization has been granted by Agennix Incorporated, procedures 
for proper disposal have been established according to applicable regulations and guidelines and 
institutional procedures, and appropriate records of the disposal have been documented 


Version Date: 05-10- 2011 
50 
 
13.2 Prednisone 
13.2.1 Chemical name and identification 
Chemical Name: Prednisone (17α,21-dihydroxypregna-1,4-diene-3,11,20-trione) is 
commercially formulated as the acetate salt (prednisone 21-acetate).     
Other Names:  
 
Classification:  
Steroids   
Mechanism of Action: 
Multiple mechanisms leading to anti-inflammatory and 
immune suppression outcomes  
Molecular Formula: C23H28O6 
 
M.W.: Prednisone molecular weight is 400.5  
13.2.2 How Supplied:   
Prednisone is supplied as a tablet or suspension.  We will use commercially available prednisone 
stock acquired by the NIH Clinical Center Pharmacy. 
13.2.3 Storage:  
Prednisone should be stored in original containers at room temperature and should be protected 
from light.  
13.2.4 Stability:  
Prednisone is stable up to 3 years.  
13.2.5 Route of Administration:  
Oral 
13.2.6 Reported Adverse Events and Potential Risks:   
 
Body as a whole:  
fatigue,  
Ophthalmic: 
cataracts, papilledema 
Hematologic: 
eosinopenia, 
leucocytosis, 
lymphopenia, 
thrombocytopenia, anemia 
Gastrointestinal:  
peptic ulcers, pancreatitis, abdominal pain 
Hepatic: 
increased bilirubin, ALT, AST, GGT, LDH, and 
alkaline phosphatase 
Metabolic and Nutritional: hyperglycemia, hyperuricemia, hypercalcemia, 
adrenal suppression, Cushing's syndrome, porphyria, 
lipid abnormalities, hypokalemia, 
Renal: 
nephrotoxicity, proteinuria 
Neurologic: 
psychosis, schizophrenic psychosis, extrapyramidal 
effects, pseudotumor cerebri, 
Cardiovascular:  
unknown 
Skin: 
acne 
Musculoskeletal: 
osteonecrosis, osteoporosis, myopathy 
 
Other: 
Superinfections 


Version Date: 05-10- 2011 
51 
 
13.2.7 Method of Administration:  Prednisone should be taken with at least 120 ml to 250 mL 
of water and should be given without food. However, if patients develop GI distress, 
dosing schedule can be modified to be taken with food. 
13.2.8 Availability 
Prednisone will be obtained from commercial stock purchased by the NIH CC Pharmacy 
Department  
13.2.9 Agent Accountability 
The investigator, or a responsible party designated by the investigator, must maintain a careful 
record of the inventory and disposition of all drugs using the NCI Drug Accountability Record 
Form (DARF).   Prednisone, as an oral self-administered investigational agent, will be properly 
accounted for, handled, and disposed in accordance with CCR Policy # Clin-1 “Policy on 
Documenting, Handling and Disposing of Oral Investigational Agents that are Self-Administered 
by NCI CCR patients.”  The Standard Operating Procedure # Clin-1 “Standard Operating 
Procedure for Conducting and Documenting Drug Accountability for Oral Investigational Agents 
that are Self Administered by Patients at the CCR” identifies all activities associated with drug 
accountability for orally self administered investigational agents.  Patients will be instructed to 
document on a study diary the daily intake of satraplatin and prednisone (Appendix C), including 
the time the dose is taken, and whether or not any doses are missed.  They will bring the study 
diary and any unused drug to their clinic appointments.  Clinic staff will (1) collect all “old” [i.e., 
empty bottle(s), partial bottle(s) or full bottle(s)] of study drug; (2) perform a capsule count and 
record the results in the electronic record, CRIS; (3) dispense the partial and full bottle(s) of 
prednisone to the patient.  Unused study drug is to be returned to the research nurse who will 
dispose of it according to the SOP. 
 


Version Date: 05-10- 2011 
52 
 
 
14 References 
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Version Date: 05-10- 2011 
55 
 
15 PERFORMANCE STATUS CRITERIA 
 
 
ECOG Performance Status Scale 
 
 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, able 
to carry on all pre-disease 
performance without restriction. 
100 
Normal, no complaints, no evidence 
of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease. 
1 
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 


Version Date: 05-10- 2011 
56 
 
 
16 Appendix B: Patients’ Pill Diary 
 
Today’s Date___________________________________ 
 
Patient Name______________________________   Patient Study ID________________ 
 
Total dose of Satraplatin (in milligrams)__________________  
 
 Cycle Number________________________ 
 
 
INSTRUCTIONS TO THE PATIENT: 
 
1. Complete one form for each cycle. 
 
2. You will take____pills of 50mg Satraplatin pill and ___ pills of 10mg Satraplatin pill 
each day on Days 1-5. You must take the pills on an empty stomach, no food for two 
hours before, or one hour after Satraplatin. Anti-nausea pill must be taken 30-60 minutes 
before Satraplatin dose. 
 
3. You will take 1 pill of Prednisone (5mg) in the morning and 1 pill of Prednisone (5mg) in 
the evening on Days 1-35. On days 1-5 when you’re on Satraplatin, the AM dose of 
prednisone must be taken 2 hours before the Satraplatin. 
 
4. Record the date, the number of pills you took, and when you took them. 
 
5. Any symptoms or observations may be noted under the COMMENTS column. 
 
6. Please bring your pill bottle and this form to your physician when you go for you next 
appointment. 


Version date: 5-10-11 
 
57 
 
17 APPENDIX C.  Study Calendar  
Schedules shown in the Study Calendar below are provided as an example and should be 
modified as appropriate (+/- 1-2 days to allow for clinic variations around federal holidays). 
 
 
 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
•
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
08-C-0074 
PRINCIPAL INVESTIGATOR: 
William Dahut, MD 
STUDY TITLE: 
A Phase II Study of Satraplatin and Prednisone in Metastatic Androgen Independent Prostate 
Cancer (AIPC) 
Continuing Review Approved by the IRB on 2/14/11 
 
Amendment Approved by the IRB on 5/18/11 (F) 
Date Posted to Web: 5/26/11 
Standard 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (1) 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary. 
You may choose not to take part, or you may withdraw from the study at any time.  In either case, you will not 
lose any benefits to which you are otherwise entitled.  However, to receive care at the NIH, you must be taking 
part in a study or be under evaluation for study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that may help people in the 
future.
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other 
health professional.   
If you are signing for a minor child, “you” refers to “your child” throughout the consent document. 
In an attempt to develop more effective treatments for cancer, we propose treating you with Satraplatin and 
prednisone.  Satraplatin is an experimental drug which may soon be approved for prostate cancer.  Prednisone has 
been approved for use in prostate cancer. 
You should understand that this study involves research.  Eligibility criteria are routinely used to assure that patients who 
enter experimental studies are medically appropriate candidates for this therapy and that they have the carefully defined 
medical condition as outlined by the study protocol.  For your own well being, as well as to ensure that the results of this 
study can be useful to making treatment decisions regarding other patients with similar diseases, it is important that no 
exceptions be made to these criteria for admission to the study.  If new information is gained regarding your disease or 
related to the drug being studied, we may discuss that information with you. 


MEDICAL RECORD 
CONTINUATION SHEET for either:
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER: 
08-C-0074 
CONTINUATION:  page 2  of  8  pages 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
Description of Research Study 
This study involves your voluntary participation in a research protocol.  The purpose of this research is to know whether 
the drug satraplatin may help treat your prostate cancer depending on the presence of specific genes.  Satraplatin is 
currently being studied in prostate cancer patients and has been found to benefit them.  This study is designed with the 
satraplatin being given along with another drug called prednisone, which is also being used for prostate cancer.  Blood 
work will be done to determine if you possess a certain type of gene called ERCC1 or its variant genes, and to see if 
possession of these genes will help make the drug work better or not.  A gene is a hereditary unit passed from parent to 
offspring. Genes are made up of pieces of DNA and most genes contain the information for making a specific protein that 
performs important functions in our body. Changes or variations in the DNA of our genes can change the function of the 
protein made by the gene. ERCC1 is a gene that helps repair damage brought about by the chemotherapy drug 
satraplatin. Blood work will be done to determine if you have any variants in your ERCC1 gene and to see whether any of 
the variants in the ERCC1 gene help make the drug work better or not. If you have an ERCC1 variant that repairs the 
damage done by the chemotherapy drug satraplatin, the drug may not work well for your prostate cancer because it will 
not be able to damage the cancer cells effectively. This study will try to determine whether this hypothesis is true or not. 
There will be other genes that we will test for including XRCC1 and PARP1.  However, these tests will be for study 
purposes only and will remain strictly confidential and results will not be disclosed to anyone. 
The drug satraplatin is currently not FDA approved yet because more time is needed to determine possible survival 
benefits, but studies have been conducted using satraplatin in tumors like lung cancer, ovarian cancer and prostate 
cancer.  Prednisone is a drug which is being used in combination with other drugs approved for prostate cancer. 
Satraplatin (a type of chemotherapy) will be taken by mouth every day for five consecutive days out of every thirty-five 
days. The Satraplatin pills (the number of pills depend on your weight and height) must be taken in the morning for 5 
straight days, with no food for 2 hours before or 1 hour after the dose.  Every 35 days constitute a “cycle”.  In addition, 
we will ask you to take a pill to prevent nausea and vomiting 1 hour before as well as taking the prednisone pill two 
times a day (morning and evening) every day while you’re on-study.   
The blood test to look for the variants in your ERCC1 gene will be done and analysis of the results will be made after 
the first 20 patients get enrolled.  For the first 3 cycles of every 35 days each, you will need to get blood drawn weekly 
either here at NIH or at your local doctor’s office to see whether  your blood counts don’t get too low since your dose of 
Satraplatin may need to be adjusted at your next cycle. 
We will repeat some of the studies (e.g., bone scan and/or CT scan) to determine if your cancer has responded 
approximately every 70 days.  If there are no severe signs of toxicity or if your cancer has not progressed we will 
continue to give you satraplatin and prednisone.  Your experimental treatment is designed to be as an outpatient (with 
the exception of the first and fifth dose of the first cycle where you may spend several nights in the Clinical Center 
Hospital).  This investigational therapy could last greater than 6 months, depending on whether you are gaining benefit 
from this experimental treatment and not experiencing side effects.   
It is possible that some of the prostate cancer cells in your body may still grow if exposed to the male hormone 
testosterone.  Thus your testosterone must be suppressed either surgically (removal of the testicles) or medically with 
an injection (shot) with a luteinizing hormone-release hormone (LHRH) agonist (leuprolide or goserelin). LHRH agonists 
are drugs that reduce the amount of the male hormone testosterone. 
Your doctors have told you that you have advanced prostate cancer that is not responding to hormonal therapy.  Your 
doctors have told you that although “standard” treatment could be administered to you, there is no known curative option 
for your cancer.  For this reason, we are offering you experimental treatment on this research study.  Although we hope 


MEDICAL RECORD 
CONTINUATION SHEET for either:
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER: 
08-C-0074 
CONTINUATION:  page 3  of  8  pages 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
that this experimental therapy may benefit you and that your disease will not progress, there is no guarantee that your 
tumor will respond.  Benefit cannot be promised, nor can the chance of benefit be accurately predicted.  Likewise, we 
cannot promise you that these drugs will not cause some side effects. 
Before receiving any form of treatment, you will be evaluated in the outpatient clinic to see if you are eligible for this 
experimental therapy. You are being offered this therapy because you have cancer of the prostate, which has been 
treated with hormone therapy or at least one type of chemotherapy, but now shows a rising PSA.  X-rays, scans, or other 
tests must show evidence for spread of the cancer (metastases).   
Your participation in this research project will be for a period of at least 3 to 6 months, although this period may be 
shorter or longer depending on the response of your tumor or if you experience serious side effects.   
The procedure for this project involves an initial evaluation in the outpatient clinic to see if you qualify for this study. This 
evaluation phase may last from several days to several weeks.  Additional blood tests will check to see if your liver, 
kidneys, and other organs are working well enough to be safe to start the treatment. Altogether these initial tests will 
require about 35 cc (2 tablespoonfuls) of blood.  Finally, before starting treatment, bone scan, x-rays or other ways of 
taking pictures of your internal organs and measuring your tumor with computerized tomography (CT scans) and/or 
magnetic resonance imaging (MRI scans) will be obtained, as well as evaluation of your heart with the electrocardiogram 
tracing (EKG). 
The treatment plan is outlined above.  If you do not experience bad side effects (see below) and if your tumor does not 
grow at the time of the first 2 cycles, the cycles will be repeated every five weeks. If you experience unacceptable side 
effects (toxicities) at any time in the study, you will not receive additional treatments on this study.  You will have your 
scans and x-rays repeated approximately every 70 days while on study.   
A total of up to 66 patients/human volunteers are expected to participate in this project. 
Risk or Discomforts of Participation 
We are asking you to participate in this study.  Both of these drugs have been given to humans and thus we have a 
good idea of the potential side effects you may develop.  The combination of both satraplatin plus prednisone has been 
administered together, thus, we can predict the side effects that you may experience based on a recently concluded 
trial that also used the same combination.  You will be monitored closely while you are receiving this experimental 
treatment for any signs that might signal the earliest stage of toxicity so that appropriate intervention can be done. 
It is extremely important that you notify us before starting to take any new medications that your local doctors may 
have prescribed, or that you may purchase over the counter at a drug store (cold medication and antacids for your 
stomach).  Satraplatin can have an interaction with several other drugs.  Thus, you should notify us if you start any 
new treatments. 
The more common side effects that have been associated with satraplatin include:   
x
decreased platelet count, decreased red blood cell count, decreased white blood cell count (neutropenia) – 
occurring in about 21% 
x
mild bruising may accompany the decreased platelet counts 
x
nausea, vomiting, diarrhea, constipation is also common, occurring at about 58% of patients 
Other less common complications include:  abdominal pain, flatulence, numbness or tingling, diarrhea, elevated liver 
enzymes, fatigue, headache, dizziness, myalgia, fever, chills, fast heart beat, syncope (fainting), low blood pressure, 


MEDICAL RECORD 
CONTINUATION SHEET for either:
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER: 
08-C-0074 
CONTINUATION:  page 4  of  8  pages 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
changes in hearing, kidney dysfunction, pain in the arms, chest, back or legs, blood clot, shortness of breath, and 
cough.
The side effects that have been associated with prednisone include:  
x
gastric hyperacidity(increased stomach acid), increased appetite, insomnia or nervousness occurring in > 10% of 
patients
x
hyperglycemia (high blood sugar level), fluid retention, mood swings, dizziness, headaches, muscle weakness, 
osteoporosis (bone thinning), and cataracts with long-term use, occurring in about 1% - 10% of patients 
x
Hypertension occurring in < 1% of patients 
The side effects that have been associated with the pill to prevent nausea or vomiting (like granisetron for prevention of 
nausea or vomiting) include: 
x
Headache (occurring around 9% - 21% of patients) 
x
Fatigue or weakness (occurring around 5% - 18% of patients) 
x
Constipation (occurring around 3% - 18% of patients) 
Less common side-effects include: hypertension, pain, dizziness,insomnia, somnolence, anxiety, agitation or stimulation, 
rash, diarrhea, abdominal pain, elevated liver enzymes, decreased urination, cough, infection which occurs in 1% to 10% 
of patients, and rare (<1%) but important or life-threatening reactions include: allergy to the drug, increased or abnormal 
heart beat, or syncope (fainting).  
We will also ask you to allow us to perform a tumor biopsy, whenever feasible, to look at the level of expression of this 
gene ERCC1 in your tumor, and correlate that with your response to the chemotherapy drug satraplatin.  We will 
coordinate with the radiologists in Special Procedures department to look at your CT Scans to see if the tumor can be 
biopsied.  A numbing medication similar to lidocaine is used prior to this procedure.  The side effects include, but are not 
limited to pain, infection and the risk of bleeding. A separate consent form will be provided to you to describe the tumor 
biopsy procedure in more detail as well as any additional side effects should you consent to the procedure.  This 
procedure is optional and consenting to the study is not contingent upon your consent to the procedure. 
Potential Benefit 
This is a phase II study, which means we are trying to determine whether the combination of the drug satraplatin and 
prednisone will be beneficial to treat your prostate cancer if you possess the variant ERCC1 gene or not. 
Benefit cannot be promised, nor can the chance of benefit be accurately predicted.  It is possible that you may 
experience some, all, or none of the side effects described above.  It is also possible that either the satraplatin or the 
prednisone may produce some unanticipated side effects.  For that reason, you will be monitored closely while you are 
receiving this experimental treatment for any signs that might signal the earliest stage of toxicity so that appropriate 
intervention can be done. 


MEDICAL RECORD 
CONTINUATION SHEET for either:
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER: 
08-C-0074 
CONTINUATION:  page 5  of  8  pages 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
Alternative Treatments 
The standard treatment for patients with metastatic prostate cancer is hormonal therapy.  However, when patients’ 
cancer continues to progress despite hormonal therapy (AIPC), there is no clear standard of therapy. Patients may be 
treated with radiotherapy, investigational agents, chemotherapy or sometimes observed.  Ketoconazole and 
hydrocortisone is sometimes used alone in this setting.  The role of chemotherapy in patients with AIPC has historically 
been questioned due to the lack of efficacy in the agents used.  However, newer agents and combinations are being 
investigated.  The combination of mitoxantrone and prednisone has shown palliative benefits.   Docetaxel and prednisone 
has shown improved overall survival benefit, as well as docetaxel and estramustine.  Satraplatin has also been used with 
prednisone and has improved progression-free survival, as presented in a major medical meeting. 
Other options include palliate care, which includes: 
x
Getting no treatment. 
x
Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite 
problems, and other problems caused by cancer. It does not treat the cancer directly, but instead tries to 
improve how you feel. Comfort care tries to keep you as active and comfortable as possible. 
Cost and Reimbursement 
If you choose to participate in this study, your medical care and the costs of the laboratory and radiographic studies done 
at the Clinical Center, National Institutes of Health will be at no charge to you.  The NIH cannot reimburse you for the 
costs of medical care delivered outside the NIH, even if you are seeking medical attention as a result of side effects of 
treatment given on this study.  Similarly, you cannot be reimbursed if you choose to have diagnostic radiographic tests 
(such as chest x-rays or CT scans) performed locally (outside of the NIH), even if they are done for the purposes of this 
study. 
Communication 
The NCI physicians involved in your care are available to answer all of your questions concerning this protocol. If you 
have any concerns or questions, you may contact Dr. William Dahut, the Principal Investigator at (301) 435-8183, or 
Associate Investigators Dr. James Gulley at (301) 435-2956, Dr. Philip Arlen at (301) 496-0629 or the research nurses, 
Lea Latham at (301) 402-9137, Marcia Mulquin at (301) 435-5613 or David Draper at (301) 435-5614.  If you have any 
complications when you are not in the Clinical Center (e.g., at home or in a local hotel), you may call the page operator 
at (301) 496-1211 and ask for either the NCI Medical Oncology Branch physician on call or the NIH Patients’ Rights 
Representative who will be available to answer questions concerning your involvement in this study or your rights as a 
research subject.  She is not directly associated with this study and can be contacted at (301) 496-2626. 
Research Subjects’ Rights 
You will be told if no benefit occurs to you as a result of taking part in this treatment program and the program will be 
stopped.
You will receive a copy of this informed consent for your own records.  In addition, a copy of the informed consent is on 
file with the Medicine Branch of the National Cancer Institute and a copy will be made available to you whenever you 
want to see it.  Your records will be kept confidential, with the exception that the FDA, the drug company that 
manufactures the appropriate study drugs may have access to your medical record, as well as the staff of the National 
Cancer Institute, and representatives of GPC Biotech, Inc. may inspect and study your medical records. 


MEDICAL RECORD 
CONTINUATION SHEET for either:
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study
STUDY NUMBER: 
08-C-0074 
CONTINUATION:  page 6  of  8  pages 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either:
NIH-2514-1 (10-84)
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
Your participation in this study is entirely voluntary, and you may refuse to participate, or withdraw from this protocol at 
any time and receive care from your referring physician. 
Your participation in this study may be ended by the Principal Investigator or an Associate Investigator without your 
consent if they feel termination is medically indicated. 
Upon completing this study, you may be given the choice of taking part in other research protocols that may be 
appropriate for you.  Otherwise, you will be returned to the care of your referring physician.  It is important to stress that 
your participation in this study does not constitute a promise of long term care at the NIH Clinical Center.  If there is no 
research study that can help you, you will be returned to the care of your private doctor.  If you do take part in this 
study, you may be unable to take part in certain other research protocols because these protocols may not allow patients 
who have been on certain drugs to enter.  You may decide now not to receive treatment in this protocol, or you may 
choose at any time to stop the drug and withdraw from the protocol.  In either case, you would be returned to the care 
of your referring physician. 
Your signature on this consent indicates that you agree to participate in this medical research study under the direction of 
the principal investigator as listed above.  In addition to your signature, please read each sentence below and think about 
your choice. After reading each sentence, circle and initial the answer that is right for you. If you have questions, please 
talk to your physician or nurse, or call the NCI’s Cancer Information Service at 1-800-422-6237 (1-800-4-CANCER) 
My tissue (specimen) may be kept for use in research to learn about, prevent, or treat cancer: 
Yes_____ No_____ Initials_____ 
My tissue (specimen) may be kept for use in research to learn about, prevent or treat other health problems (for 
example: diabetes, Alzheimer’s disease, or heart disease). 
Yes_____ No_____ Initials_____ 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
•
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
08-C-0074 
CONTINUATION: page  7  of  8  pages 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet)
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
OTHER PERTINENT INFORMATION 
1. Confidentiality.  When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified.  In most cases, the NIH will not release any information 
about your research involvement without your written permission.  However, if you sign a release of information 
form, for example, for an insurance company, the NIH will give the insurance company information from your medical 
record.  This information might affect (either favorably or unfavorably) the willingness of the insurance company to 
sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you should know that the 
Act allows release of some information from your medical record without your permission, for example, if it is 
required by the Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized 
hospital accreditation organizations. 
2. Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here.  In general, no long-term medical care or financial 
compensation for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or 
the Federal Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies 
such action. 
3. Payments.  The amount of payment to research volunteers is guided by the National Institutes of Health policies.  In 
general, patients are not paid for taking part in research studies at the National Institutes of Health. Reimbursement 
of travel and subsistence will be offered consistent with NIH guidelines. 
4. Problems or Questions.  If you have any problems or questions about this study, or about your rights as a 
research participant, or about any research-related injury, contact Dr. William Dahut, the Principal Investigator at 
(301) 435-8183, or Associate Investigators Dr. James Gulley at (301) 435-2956, or Dr. Philip Arlen at (301) 496-0629.  
You may also call the Clinical Center Patient Representative at 301-496-2626. 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
•
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 
08-C-0074 
CONTINUATION: page  8  of  8  pages 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
(Continuation Sheet)
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby consent to take 
part in this study. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby give permission 
for my child to take part in this study.   
(Attach NIH 2514-2, Minor’s Assent, if applicable.) 
Signature of Adult Patient/Legal Representative 
Date 
Print Name 
Signature of Parent(s)/Guardian 
Date 
Print Name 
C. Child’s Verbal Assent (If Applicable)
The information in the above consent was described to my child and my child agrees to participate in the study.
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM FEBRUARY 14, 2011 THROUGH FEBRUARY 13, 2012.  
Signature of Investigator 
Date 
Print Name 
Signature of Witness 
Date 
Print Name