Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Indiana University
Sponsor:
Collaborator:
Ziopharm
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT01808534
First received: March 6, 2013
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
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
Drug: palifosfamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Rate of response (CR+PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and/or serum tumor markers (alpha fetoprotein and beta-hCG) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized in the evaluable population by proportions with 90% confidence intervals.


Secondary Outcome Measures:
  • Rate of CR [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized in the evaluable population by proportions with 90% confidence intervals.

  • Rate of PR [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized in the evaluable population by proportions with 90% confidence intervals.

  • Duration of remission (CR + PR) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley.

  • Progression free survival (PFS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley.

  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier methods including 90% confidence intervals for the median using method of Brookmeyer and Crowley.

  • Continuous disease-free survival rate at 12 months post-treatment initiation [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
  • Adverse event rates, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Tolerability will be summarized by the appropriate statistics of safety measures, including grade 3/4 toxicity rates. Counts and proportions by toxicity will be presented with exact binomial 90% confidence intervals. Counts and proportions of overall toxicity by patient, defined as experience of at least 1 grade 3/4 toxicity, will be calculated with exact binomial 90% confidence intervals. Relation of toxicity to treatment regimen will be presented by counts and proportions.


Estimated Enrollment: 20
Study Start Date: February 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01808534

Contacts
Contact: M. Jackie Brames, RN 317-944-7929 mjbrames@iupui.edu
Contact: Lawrence H Einhorn, MD 317-948-4312 leinhorn@iupui.edu

Locations
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: M. Jackie Brames, RN    317-944-7929    mjbrames@iupui.edu   
Contact: Lawrence H. Einhorn, MD    317-948-4312    leinhorn@iupui.edu   
Principal Investigator: Lawrence H. Einhorn         
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David J. Vaughn    215-349-8140    david.vaughn@uphs.upenn.edu   
Contact: Anja M Jones, MS    215-349-8152    Anja.Jones@uphs.upenn.edu   
Principal Investigator: David J. Vaughn         
United States, Washington
Virginia Mason Medical Center Not yet recruiting
Seattle, Washington, United States, 98101
Contact: Craig R. Nichols    206-223-6193    craig.nichols@vmmc.org   
Principal Investigator: Craig R. Nichols         
Sponsors and Collaborators
Indiana University School of Medicine
Ziopharm
Investigators
Principal Investigator: Lawrence H Einhorn, MD Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT01808534     History of Changes
Other Study ID Numbers: IUCRO-0403, NCI-2013-00510, 1301010501
Study First Received: March 6, 2013
Last Updated: July 16, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Testicular Diseases
Seminoma
Teratoma
Testicular Neoplasms
Neoplasms, Germ Cell and Embryonal
Germinoma
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Gonadal Disorders
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Ifosfamide
Isophosphamide mustard
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014