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Melphalan, Carboplatin, and Sodium Thiosulfate for Patients With Central Nervous System (CNS) Embryonal or Germ Cell Tumors

Information source: OHSU Knight Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Central Nervous System Embryonal Tumor; Germ Cell Tumors

Intervention: Melphalan (Drug); Carboplatin (Drug); Sodium thiosulfate (Drug); Filgrastim (Drug); Pegfilgrastim (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: OHSU Knight Cancer Institute

Official(s) and/or principal investigator(s):
Edward A Neuwelt, MD, Principal Investigator, Affiliation: Oregon Health and Science University

Overall contact:
Edward A Neuwelt, MD, Phone: 503-494-5626, Email: neuwelte@ohsu.edu

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.

Clinical Details

Official title: Phase I/II Study of Intra-arterial Melphalan Given With Intra-arterial Carboplatin, Osmotic Blood-Brain Barrier Disruption and Delayed Otoprotective Sodium Thiosulfate for Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: PHASE I: PRIMARY OBJECTIVE To determine the maximum tolerated dose (MTD) of IA melphalan given with IA carboplatin, osmotic BBBD and delayed IV STS in subjects with recurrent or progressive embryonal and germ cell tumors of the CNS.

Secondary outcome:

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.

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.

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.

Eligibility

Minimum age: 1 Year. Maximum age: 30 Years. Gender(s): 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 and Contacts

Edward A Neuwelt, MD, Phone: 503-494-5626, Email: neuwelte@ohsu.edu

University of Minnesota, Minneapolis, Minnesota 55455, United States; Recruiting
Dan Guillaume, MD, Phone: 612-624-5931, Email: dguillau@umn.edu
Tammie Dahlheimer, NP, Phone: 612-626-2629, Email: tdahlheimer@umphysicians.umn.edu
Dan Guillaume, MD, Sub-Investigator

Oregon Health & Science University, Portland, Oregon 97239, United States; Recruiting
Edward A Neuwelt, MD, Phone: 503-494-5626, Email: neuwelte@ohsu.edu
Amy Huddleston, Phone: 503-494-0051, Email: huddlesa@ohsu.edu
Edward A Neuwelt, MD, Principal Investigator

Additional Information

Starting date: September 2009
Last updated: May 8, 2015

Page last updated: August 23, 2015

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