Melphalan, Carboplatin, and Sodium Thiosulfate for Patients With Central Nervous System (CNS) Embryonal or Germ Cell Tumors
Conditions
Central Nervous System Embryonal Tumor - Germ Cell Tumors
Conditions: official terms
Neoplasms - Neoplasms, Germ Cell and Embryonal
Conditions: Keywords
CNS embryonal tumor, cognitive/functional effects, drug toxicity, response rate, survival times, maximum tolerated dose (MTD) of IA melphalan/IA carboplatin, 2-year progression-free survival (PFS) and overall survival (OS) rates
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Melphalan Type: Drug
Name: Carboplatin Type: Drug
Name: Sodium thiosulfate Type: Drug
Name: Filgrastim Type: Drug
Name: Pegfilgrastim Type: Drug
Overall Status
Recruiting
Summary
- The purpose of this study is to determine the safety and effectiveness of the chemotherapy drugs called carboplatin and melphalan, when they are given into an artery, in patients with malignant brain tumors (called embryonal and germ cell tumors). The carboplatin and melphalan will be given during a procedure called blood-brain barrier disruption (BBBD). When used to treat this type of brain tumor, BBBD treatment is experimental and not approved by the FDA. Patients also receive a drug called sodium thiosulfate in a vein, in order to protect against carboplatin-induced hearing loss.

- Participants will be admitted to the hospital every four weeks for approximately three days. The patient will be put to sleep with general anesthesia, and a tube will be placed in an artery in the groin. Mannitol (a sugar solution) will be given into the tube in the groin artery; this procedure is called blood-brain barrier disruption (BBBD). Next, the carboplatin and melphalan chemotherapy drugs will be given into the artery. The BBBD procedure is done on two days in a row, every four weeks. The patient will undergo monthly MRI scans of the head, monthly hearing evaluation, as well as weekly blood tests. The patient will also have memory testing done. Treatment will last for up to 12 months.
Detailed Description
PHASE I PRIMARY OBJECTIVE To determine the maximum tolerated dose (MTD) of Intra-arterial (IA) melphalan given with IA carboplatin, osmotic BBBD and delayed IV sodium thiosulfate (STS) in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS.

PHASE II PRIMARY OBJECTIVE To estimate the response rate in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS.

SECONDARY OBJECTIVES

- To describe 2-year progression-free survival (PFS) and overall survival (OS) rates in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS.

- To describe neuropsychological and audiology outcomes in subjects with recurrent or progressive CNS embryonal and germ cell tumors treated with IA carboplatin, IA melphalan, osmotic BBBD and delayed IV STS.

- To describe the overall toxicity of IA carboplatin and IA melphalan in conjunction with osmotic BBBD and delayed STS chemoprotection in subjects with recurrent or progressive CNS embryonal or germ cell tumors.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 30 Years
Minimum Age: 1 Year
Gender: Both
Criteria: Inclusion Criteria:

- Subjects with histologically confirmed CNS embryonal tumor (PNET, medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT), medulloepithelioma, pineoblastoma or ependymoblastoma), or germ cell tumor

- Subjects must have had prior therapy according to the best available therapy as determined by their primary brain tumor specialist (to include oncology, neurosurgery and/or radiation oncology) including systemic and/or cranial radiation or chemotherapy. At least 14 days must have elapsed since completion of cranial radiotherapy and 28 days since completion of chemotherapy. At least 28 days must have elapsed since completion of total spine radiotherapy

- Subjects must have a consultation with a radiation oncologist or providers must have a discussion in the context of Neuro-Oncology Tumor Board within 28 days prior to start of IA/BBBD chemotherapy to determine the need for radiotherapy prior to or after IA/BBBD.

- For the phase II portion of the study, subjects must have disease that is evaluable for response per Section 8.4. Subjects who have had radiation to all sites of disease are not eligible unless there has been documented radiographic progression of tumors subsequent to radiation

- Age greater or equal to 1 year and less than 30 years of age

- Baseline laboratory data should be the following:

- Glomerular filtration rate (GFR) greater than 30

- Absolute granulocyte count greater or equal to 1.0 x 103/mm3

- Platelets greater or equal to 100 x 103/mm3

- Creatinine < 1.5

- Total Bilirubin < 2.0

- Aspartate aminotransferase-Alanine aminotransferase (AST/ALT) < 2.5x upper limits of normal

- Karnofsky Performance Status (KPS) must be greater than or equal to 50%

- Subjects or their legal guardian must sign a written informed consent in accordance with institutional guidelines

- Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study treatment and for the duration of study treatment.

Exclusion Criteria:

- radiographic signs of excessive intracranial mass effect with associated rapid neurologic deterioration and/or spinal cord block

- significant risk with general anesthesia

- uncontrolled (over the last 30 days) clinically significant confounding medical conditions

- pregnant or lactating

- contraindications to carboplatin, melphalan, or STS
Locations
University of Minnesota
Minneapolis, Minnesota, United States
Status: Recruiting
Contact: Dan Guillaume, MD - 612-624-5931 - dguillau@umn.edu
Oregon Health & Science University
Portland, Oregon, United States
Status: Recruiting
Contact: Edward A Neuwelt, MD - 503-494-5626 - neuwelte@ohsu.edu
Start Date
September 2009
Completion Date
December 2016
Sponsors
OHSU Knight Cancer Institute
Source
OHSU Knight Cancer Institute
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page