Combination Chemotherapy With BBBD Followed By Sodium Thiosulfate in Treating Patients With Anaplastic Oligodendroglioma or Oligoastrocytoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00303849
First received: March 15, 2006
Last updated: May 2, 2014
Last verified: May 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as etoposide, carboplatin, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Chemoprotective drugs, such as sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Blood-brain barrier disruption uses certain drugs, such as mannitol, to open the blood vessels around the brain and allow chemotherapy to be carried directly to the brain tumor. Giving combination chemotherapy together with blood-brain barrier disruption may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with etoposide, carboplatin and blood-brain barrier disruption followed by sodium thiosulfate and to see how well they work in treating patients with anaplastic oligodendroglioma or oligoastrocytoma.


Condition Intervention Phase
Anaplastic Oligodendroglioma
Mixed Oligoastrocytoma
Brain and Central Nervous System Tumors
Drug: Etoposide phosphate
Drug: Melphalan
Drug: Carboplatin
Drug: Sodium thiosulfate
Drug: Filgrastim
Drug: Pegfilgrastim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Carboplatin, Melphalan and Etoposide Phosphate in Conjunction With Osmotic Opening of the Blood-Brain Barrier and Delayed Intravenous Sodium Thiosulfate Chemoprotection, in Previously Treated Subjects With Anaplastic Oligodendroglioma or Oligoastrocytoma

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of melphalan as measured by NCI Common Terminology Criteria (CTC) v3 (Phase I) [ Time Frame: Completed ] [ Designated as safety issue: Yes ]

    MTD = 1 dose level below dose level that produces grade 4 toxicity attributable to the chemotherapy regimen that occurs during cycle one of chemotherapy, in 33% of subjects.

    The Melphalan MTD when given with this combination chemotherapy has been determined to be 4mg/m2/day x 2 days.


  • Progression-free survival as measured by radiographic response at one year progression free survival (1YPFS) (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of neutropenia as measured by complete blood cell count lab values done weekly during study treatment [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Evaluate incidence of severe neutropenia (febrile neutropenia or sepsis) of carboplatin, melphalan, and etoposide phosphate in conjunction with BBBD

  • Overall toxicity of chemotherapy as measured by NCI CTC v3 during study treatment [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Estimate differences in tumor response, 1YPFS, and survival in patients with and without allelic loss as measured by lab assays before study treatment [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Evaluation of allelic loss by lab assays testing for chromosomes 1p and 19q and p53 immunocytochemistry

  • Quality of life (QOL) as measured by European Organisation for Research and Treatment of Cancer (EORTC) QOL [ Time Frame: Up to 3 years plus follow up ] [ Designated as safety issue: No ]
    Every 3 months during treatment and within 30 days of final treatment. After final treatment, QOL assessment annually.

  • Estimate differences in 1YPFS between subjects with anaplastic oligodendroglioma and oligoastrocytoma [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Describe role of biopsy vs extent of surgery on 1YPFS and survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Role of biopsy versus extent of surgery (sub-maximal versus maximal safe resection)on 1YPFS and survival

  • Role of prior radiation on tumor response, 1YPFS, and survival. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Describe role of prior radiation on tumor response, 1YPFS, and survival.


Estimated Enrollment: 60
Study Start Date: September 2005
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects Drug: Etoposide phosphate

Dose: 200mg/m2/day x 2 days; Every 4 weeks for up to one year

Etoposide may be substituted

Drug: Melphalan
Dose: 4mg/m2/day x 2 days; Every 4 weeks for up to one year.
Drug: Carboplatin
Dose: 200mg/m2/day x 2 days; Every 4 weeks for up to one year
Drug: Sodium thiosulfate

Dose: 4 hrs post carboplatin = 20gm/m2

Dose: 8 hrs post carboplatin = 16gm/m2

Every 4 weeks for up to one year

Other Name: STS
Drug: Filgrastim

48 hrs after last dose of carboplatin, every day (QD) x 7-10 days until white blood cells (WBC) greater than 5000. Dose based on weight of subject.

Pegfilgrastim (Neulasta) may be given instead.

Other Names:
  • G-CSF
  • Neupogen
Drug: Pegfilgrastim

Dose: 6mg, 24-72 hrs after chemotherapy.

Filgrastim (Neupogen) may be given instead

Other Names:
  • G-CSF
  • Neulasta

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate toxicity and estimate the maximum tolerated dose (MTD) of melphalan administered in conjunction with carboplatin and etoposide phosphate in combination with blood-brain barrier disruption (BBBD) with mannitol and delayed sodium thiosulfate, in patients with anaplastic oligodendroglioma or oligoastrocytoma. (phase I)
  • Examine the efficacy, in terms of 1-year progression-free survival (1YPFS), in patients treated with this regimen. (phase II)

Secondary

  • Evaluate the incidence of severe neutropenia (specifically febrile neutropenia or sepsis) in patients treated with this regimen.
  • Evaluate the overall toxicity of this regimen.
  • Compare tumor response, 1YPFS, and survival in patients with vs without allelic loss of chromosomes 1p and 19q and p53 immunocytochemistry.
  • Assess quality of life, cognitive function, and performance status in these patients.
  • Estimate differences in 1YPFS between patients with anaplastic oligodendroglioma and patients with oligoastrocytoma.
  • Describe the role of biopsy versus extent of surgery (sub-maximal versus maximal safe resection) on 1YPFS and survival.
  • Describe the role of prior radiotherapy on tumor response, 1YPFS, and survival.

OUTLINE: This is a multi-center, phase I dose-escalation study of melphalan followed by a phase II study.

  • Phase I: Patients receive etoposide phosphate IV over 10 minutes, mannitol intra-arterially (IA), carboplatin IA over 10 minutes, and melphalan IA over 10 minutes on days 1 and 2 and sodium thiosulfate IV over 15 minutes beginning 4 and 8 hours after completion of chemotherapy on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 4 and continuing until blood counts recover OR a small dose of pegfilgrastim SC on day 2. Treatment repeats every 4 weeks for up to 12 monthly courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive etoposide phosphate, mannitol, carboplatin, melphalan at the MTD, sodium thiosulfate, and G-CSF or pegfilgrastim as in phase I. Treatment repeats every 4 weeks for up to 12 monthly courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for one year; every 6 months for the next two years; then annually.

PROJECTED ACCRUAL: Up to 60 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Signed written informed consent in accordance with institutional guidelines
  • Histologically confirmed anaplastic oligodendroglioma or mixed glioma (i.e., oligoastrocytoma) (At least 25% of oligodendroglial element required to qualify as a mixed tumor)
  • Must have undergone prior surgical procedure, either complete resection, partial resection, or biopsy
  • Prior treatment with temozolomide required and at least 28 days since prior temozolomide
  • Radiation therapy: prior consultation OR at least 14 days since completion of radiation
  • Age 18-75 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS ≥ 50%
  • WBC ≥ 2,500/mm^3
  • Absolute granulocyte count > 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine < 1.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN
  • Serum glutamic oxaloacetic transaminase/Serum glutamic-pyruvic transaminase (SGOT/SGPT) < 2.5 times ULN
  • Fertile patients must use effective contraception prior to and during study treatment

EXCLUSION CRITERIA:

  • Radiographic signs of excessive intracranial mass effect and/or spinal cord block
  • Significant risk for general anesthesia
  • Uncontrolled clinically significant confounding medical condition within the past 30 days
  • Pregnant, positive human chorionic gonadotropin (HCG) or lactating
  • Contraindications to carboplatin, melphalan, etoposide phosphate, or sodium thiosulfate
  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: NCT00303849

Contacts
Contact: Edward A Neuwelt, MD 503-494-5626 neuwelte@ohsu.edu
Contact: Cynthia A Lacy, BSN 503-494-5626 lacyc@ohsu.edu

Locations
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matthew Hunt, MD    612-626-0975    huntx188@umn.edu   
Contact: Natalie Brandt, BSN    612-624-8117    nbrandt10@umphysicians.umn.edu   
Principal Investigator: Matthew Hunt, MD         
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea    503-494-1080    trials@ohsu.edu   
Contact: Edward A Neuwelt, MD    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A Neuwelt, MD         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Edward A. Neuwelt, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00303849     History of Changes
Other Study ID Numbers: OHSU-2868, P30CA069533, 8507, SOL-04058-L, 2868
Study First Received: March 15, 2006
Last Updated: May 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by OHSU Knight Cancer Institute:
adult anaplastic oligodendroglioma
adult oligoastrocytoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Oligodendroglioma
Astrocytoma
Neoplasms by Site
Neoplasms
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide phosphate
Carboplatin
Etoposide
Melphalan
Sodium thiosulfate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 22, 2014