Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

Combination Chemotherapy in Treating Children With Refractory Childhood Brain Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 21 and under NCI, Pharmaceutical / Industry ALK-01-036 NCI-96-C-0068C

Objectives

I.  Estimate the maximum tolerated dose of RMP-7 (a bradykinin analogue) that 
can be given in combination with carboplatin (CBDCA) in pediatric patients 
with refractory brain tumors.

II.  Describe and define the toxic effects associated with this treatment.

III.  Define the plasma pharmacokinetics of CBDCA when administered with RMP-7.

IV.  Determine the activity of RMP-7/CBDCA against these tumors.

Entry Criteria

Disease Characteristics:

Histologically confirmed brain tumor including but not limited to the
following:
  Anaplastic astrocytoma       Glioblastoma multiforme
  Low-grade glioma             Ependymoma
  Medulloblastoma              Pineal tumors
  Chiasmal glioma              Craniopharyngioma
  Brain stem glioma (requirement for histologic diagnosis may be waived)

Disease refractory to standard therapy or no standard chemotherapy exists and
ineligible for potential curative surgery or radiotherapy

Measurable or evaluable disease on radiographic studies with evidence of
progression on prior chemotherapy or radiotherapy or persistent disease after
surgery

Prior/Concurrent Therapy:

Biologic therapy:
 At least 3 weeks since stem cell or bone marrow rescue after nitrosoureas and
  recovered

Chemotherapy:
 See Disease Characteristics
 At least 6 months since carboplatin
 At least 6 weeks since nitrosoureas (except as specified in Biologic therapy)
 At least 3 weeks since other myelosuppressive therapy and recovered

Endocrine therapy:
 Concurrent steroids allowed if dose stable for at least 2 weeks prior to
  entry

Radiotherapy:
 See Disease Characteristics
 Recovered from any prior radiotherapy

Surgery:
 See Disease Characteristics
 Recovered from any prior surgery

Patient Characteristics:

Age:
  21 and under

Performance status:
  ECOG 0-2

Life expectancy:
  At least 8 weeks

Hematopoietic:
  Absolute granulocyte count greater than 1,500/mm3
  Platelet count greater than 100,000/mm3 (at least 75,000/mm3 in patients
   with prior bone marrow transplantation or craniospinal irradiation)
  Hemoglobin greater than 8.0 g/dL

Hepatic:
  Bilirubin no greater than 2 times normal
  ALT no greater than 2 times normal

Renal:
  Creatinine within normal limits for age as follows:
     Age (in years)           Creatinine (in mg/dL)
      younger than 5           no greater than 1.2
      5-10                     no greater than 1.5
      10-15                    no greater than 1.8
      older than 15            no greater than 2.4

Other:
  No significant systemic illness
  No pregnant or nursing women
     Negative pregnancy test required of fertile women
  Effective contraception required of fertile patients
  Durable power of attorney required of all patients 18-21 years of age

Expected Enrollment

It is anticipated that 30 patients will be entered over 1-2 years.

Outline

2-Drug Combination Chemotherapy.  RMP-7; Carboplatin, CBDCA, NSC-241240.

Warren K, Gervais A, Aikin A, et al.: Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors. Cancer Chemother Pharmacol 54 (3): 206-12, 2004.[PUBMED Abstract]

Warren KE, Patel MC, Aikin AA, et al.: Phase I trial of lobradimil (RMP-7) and carboplatin in children with brain tumors. Cancer Chemother Pharmacol 48 (4): 275-82, 2001.[PUBMED Abstract]

Warren KE, Patel MC, Adamson PC, et al.: Phase I trial of RMP-7 and carboplatin in pediatric patients with brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A-764, 1998.

Trial Contact Information

Trial Lead Organizations

Alkermes, Incorporated

Frank Balis, MD, Protocol chair		Ph: 301-496-0085 Email: balisf@nih.gov