Know Cancer

or
forgot password

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


Phase 1/Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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


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.

Inclusion 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

- 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

- 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 HCG or lactating

- Contraindications to carboplatin, melphalan, etoposide phosphate, or sodium
thiosulfate

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose (MTD) of melphalan as measured by NCI CTC v3 (Phase I)

Outcome Description:

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.

Outcome Time Frame:

Completed

Safety Issue:

Yes

Principal Investigator

Edward A. Neuwelt, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute

Authority:

United States: Institutional Review Board

Study ID:

OHSU-2868

NCT ID:

NCT00303849

Start Date:

September 2005

Completion Date:

December 2014

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic oligodendroglioma
  • adult oligoastrocytoma
  • recurrent adult brain tumor
  • Nervous System Neoplasms
  • Oligodendroglioma
  • Central Nervous System Neoplasms

Name

Location

Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
University of MinnesotaMinneapolis, Minnesota  55455
Good Samaritan Hospital Cancer Treatment Center, Hatton InstituteCincinnati, Ohio  45220