Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

Study Overview
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Brief Summary
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This phase II trial studies how well palifosfamide works in treating patients with recurrent germ cell tumors. Drugs used in chemotherapy, such as palifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the response rate (complete response [CR]+partial response [PR]) of single agent palifosfamide in patients with refractory germ cell tumors. SECONDARY OBJECTIVES: I. To determine the duration of remission. II. To determine progression free and overall survival. III. To assess toxicity and tolerability of palifosfamide in patients with germ cell tumors. OUTLINE: Patients receive palifosfamide intravenously (IV) over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors

Conditions
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Adult Central Nervous System Germ Cell Tumor, Adult Teratoma, Malignant Extragonadal Germ Cell Tumor, Malignant Extragonadal Non-Seminomatous Germ Cell Tumor, Extragonadal Seminoma, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Ovarian Germ Cell Tumor, Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor, Stage IV Extragonadal Seminoma, Stage IV Ovarian Germ Cell Tumor

Intervention / Treatment
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* Drug: palifosfamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histological or serological proof of metastatic germ cell neoplasm (gonadal or extragonadal primary) with disease not amenable to cure with either surgery or chemotherapy; patients with seminoma and nonseminoma are eligible, as are women with ovarian germ cell tumors Patients must have evidence of recurrent or metastatic carcinoma by one or more of the criteria specified in the protocol Patients must have received initial cisplatin based combination therapy (such as bleomycin, etoposide and cisplatin [BEP], etoposide and cisplatin [EP], VP-16 plus ifosfamide plus cisplatin [VIP] or similar regimens) AND demonstrated progression following the administration of at least one 'salvage' regimen for advanced germ cell neoplasm (such as high dose chemotherapy, paclitaxel/ifosfamide/cisplatin [TIP] or vinblastine, ifosfamide and cisplatin [VeIP]) Patients must have documented failure of prior therapy as defined in the protocol Patients are eligible after first line platinum based chemotherapy if their disease has relapsed and they have primary mediastinal non seminomatous germ cell tumor (PMNSGCT) or late relapse (> 2 years) not amenable to surgical resection Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Laboratory test results must be within ranges established in the protocol Potential subject must have the ability to understand (as judged by the treating physician) and willingness to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; Females of childbearing potential must not be pregnant or breast-feeding; male and female patients of reproductive potential must agree to use a highly reliable method of birth control from the screening visit through 28 days after the last dose of study drug Exclusion Criteria: No active clinically serious infections as judged by the treating investigator (> CTCAE grade 2) including known human immunodeficiency virus (HIV) infection or chronic active hepatitis B or active hepatitis C No presence of, or history of any illness or injury to the urinary tract which may make the patient more susceptible to acute renal insufficiency in the case of potential renal adverse events Patients must not have any cardiac disorders as defined in the protocol No history of psychiatric illness/social situations that would limit compliance with study requirements Patients must be at least 4 weeks post major surgery or significant traumatic injury at time of study registration Patients must be at least 7 days post any minor surgical procedure, excluding placement of a vascular access device at the time of study registration Patients must not have a known sensitivity to any component of palifosfamide or its known excipients Patients with active central nervous system (CNS) metastases are excluded Patients must not have previously been exposed to palifosfamide Patients must have at least 3 weeks after previous radiotherapy or chemotherapy and have recovered from all major toxicities (except alopecia or grade 1 or 2 neuropathy) at the time of registration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (palifosfamide)<br>Patients receive palifosfamide IV over 30 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: palifosfamide<br>* Given IV<br>* Other names: ZIO-201;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (Defined as Partial Response or Complete Response) | The percent of patients who were shown as having a partial remission or better based on definitions of response in RECIST 1.1. At least a 30% decrease in the sum of the diameters of target lesions, in reference to baseline sum diameters, needs to be confirmed to be considered as partial response or better. Note: There were no patients with a partial or complete response. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Remission in Patients Who Achieve a Partial or Complete Response | The duration of remission is from the time of confirmed partial or complete response until progression or death. Patients continuing in remission at the end of the study will be treated as censored. Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Note: There were no patients who achieved partial or complete response. | Up to 2 years | 
| Progression Free Survival (PFS) | Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis. | Up to 2 years | 
| Overall Survival | Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis at their last known alive date. | Up to 2 years | 
| Treatment Related Adverse Events Grade 3 or Higher | Number of unique patients who had a treatment related (possible, probable or definite) adverse event that was graded 3 or greater according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. | Up to 2 years |