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

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00983398

Purpose

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.

Condition	Intervention	Phase
Central Nervous System Embryonal Tumor Germ Cell Tumors	Drug: Melphalan Drug: Carboplatin Drug: Sodium thiosulfate Drug: Filgrastim Drug: Pegfilgrastim	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Sodium thiosulfate Carboplatin Filgrastim Granulocyte colony-stimulating factor Pegfilgrastim Melphalan Sarcolysin Melphalan hydrochloride Sodium hyposulfite

U.S. FDA Resources

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	55
Study Start Date:	September 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Intervention Details:

intra-arterial

Dose Level / Dose

4 mg/m2 daily X 2 days (8 mg/m2/course)
6 mg/m2 daily X 2 days (12 mg/m2/course)
8 mg/m2 daily X 2 days (16 mg/m2/course)
10 mg/m2 daily X 2 days (20 mg/m2/course)

intra-arterial 200mg/m2/day x 2 days

20 gm/m2 at 4 hours post carboplatin

16 gm/m2 at 8 hours post carboplatin

5 micrograms/kg/day SC beginning 24-48 hrs after chemotherapy

6 mg SC 24-48 hrs after chemotherapy

Detailed Description:

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.

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

Ages Eligible for Study:	1 Year to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with histologically confirmed CNS embryonal tumor (PNET, medulloblastoma, ATRT, medulloepithelioma, pineoblstoma 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:
- 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
- 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00983398

Contacts

Contact: Edward A Neuwelt, MD	503-494-5626	neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA	503-494-5626	hedrickn@ohsu.edu

Locations

United States, Oregon
Oregon Health & Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Contact: Nancy A Hedrick, BA 503-494-5626 hedrickn@ohsu.edu
Principal Investigator: Edward A Neuwelt, MD

Sponsors and Collaborators

Oregon Health and Science University

Investigators

Principal Investigator:

Edward A Neuwelt, MD

Oregon Health and Science University

More Information

No publications provided

Responsible Party:	Oregon Health & Science University ( Edward A. Neuwelt, M.D., Professor )
Study ID Numbers:	OHSU-5056, OHSU SOL-08131-L
Study First Received:	September 23, 2009
Last Updated:	September 23, 2009
ClinicalTrials.gov Identifier:	NCT00983398 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:

CNS embryonal tumor
cognitive/functional effects
drug toxicity
response rate

survival times
cognitive/functional effects
maximum tolerated dose (MTD) of IA melphalan/IA carboplatin
2-year progression-free survival (PFS) and overall survival (OS) rates

Additional relevant MeSH terms:

Anti-Infective Agents
Melphalan
Antioxidants
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Sodium thiosulfate
Carboplatin
Protective Agents
Immunosuppressive Agents

Pharmacologic Actions
Anti-Bacterial Agents
Neoplasms
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Myeloablative Agonists
Chelating Agents
Antitubercular Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Antidotes

ClinicalTrials.gov processed this record on February 08, 2010