Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

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

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

Study Overview

• Status: Terminated
• Conditions: Stage IV Ovarian Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor
• Intervention / Treatment: Drug: palifosfamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (palifosfamide); 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; Given IV; Other Names: IPM-lysine; isophosphoramide mustard-lysine; ZIO-201

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indiana University School of Medicine
• Collaborators: Alaunos Therapeutics
• Investigators: Principal Investigator: Lawrence H Einhorn, MD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 7, 2013
• First Posted (Estimate): March 11, 2013

Study Record Updates

• Last Update Posted (Estimate): July 2, 2015
• Last Update Submitted That Met QC Criteria: June 11, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Neoplasms; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Recurrence; Ovarian Neoplasms; Teratoma; Seminoma; Germinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Ifosfamide; Isophosphamide mustard
• Other Study ID Numbers: IUCRO-0403; NCI-2013-00510 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 1301010501 (Other Identifier: Indiana University Institutional Review Board)