Radiation Therapy Plus Carboplatin and Lobradimil in Treating Children With Newly Diagnosed Brain Stem Gliomas

Phase I Study of Concurrent Cereport and Carboplatin With Radiation Therapy for Children With Newly-Diagnosed Brain Stem Gliomas

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as carboplatin and lobradimil may make the tumor cells more sensitive to radiation therapy.

PURPOSE: Phase I trial to study the effectiveness of combining radiation therapy with carboplatin and lobradimil in treating children who have newly diagnosed brain stem gliomas.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Drug: cereport

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated duration of lobradimil plus carboplatin with radiotherapy in patients with newly diagnosed brain stem gliomas.
• Determine the toxic effects of this treatment regimen in these patients.
• Assess the response to radiotherapy in patients treated with this regimen.

OUTLINE: Patients receive radiotherapy for 5 consecutive days a week for 6.5 weeks, for a total of 33 doses. Patients receive carboplatin IV over 15 minutes followed by lobradimil IV over 10 minutes concurrently with radiotherapy.

The first cohort of 3-6 patients receives treatment with carboplatin and lobradimil for the first three weeks of radiotherapy, with the duration of chemotherapy increasing by one week with each subsequent cohort until the maximum duration of 6.5 weeks is reached or until unacceptable toxicity occurs in 2 of 6 patients.

Patients are followed at 6 weeks; every 3 months for 2 years; every 6 months for 3 years; and then annually thereafter.

PROJECTED ACCRUAL: A total of 15-24 patients will be accrued for this study within 36 months.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027-0700
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford
    • San Francisco, California, United States, 94143-0128
      • UCSF Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Clinical Cancer Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Children's Hospital Medical Center - Cincinnati
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Doernbecher Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Newly diagnosed diffuse, intrinsic brain stem gliomas
• Measurable disease
• No disseminated disease at sites other than brain stem
• No neurofibromatosis

• Treatment must begin within 31 days of diagnosis

  • Date of diagnosis will be considered date of surgery in patients undergoing surgical biopsy

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Karnofsky 50-100% (over 10 years of age)
• Lansky 50-100% (10 years of age and under)

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGPT no greater than 2.5 times ULN (4.0 times ULN with antiepileptic or steroid medications)

Renal:

• Creatinine less than ULN for age OR
• Creatinine clearance or glomerular filtration rate greater than 80 mL/min

Other:

• No history of severe allergic reaction to any platinum-containing compound
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors during therapy with carboplatin

Chemotherapy

• Not specified

Endocrine therapy

• Prior corticosteroids for brain stem glioma are allowed

Radiotherapy

• Not specified

Surgery

• Prior surgery for brain stem glioma is allowed

Other

• At least 24 hours since any of the following medications:

  • Vasodilating compounds
  • Angiotensin-converting enzyme inhibitors
  • Calcium channel blockers
  • Beta blockers
• No other prior therapy for brain stem glioma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 20 Days	Drug: carboplatin; Other Names: CBDCA; Paraplatin; NSC #241240; Radiation: radiation therapy; Drug: cereport; Other Names: labradimil; IND #60315
Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 25 Days	Drug: carboplatin; Other Names: CBDCA; Paraplatin; NSC #241240; Radiation: radiation therapy; Drug: cereport; Other Names: labradimil; IND #60315
Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 30 Days	Drug: carboplatin; Other Names: CBDCA; Paraplatin; NSC #241240; Radiation: radiation therapy; Drug: cereport; Other Names: labradimil; IND #60315
Experimental: Radiation Therapy, 33 Doses; Carboplatin 35mg^m2 for 33 Days	Drug: carboplatin; Other Names: CBDCA; Paraplatin; NSC #241240; Radiation: radiation therapy; Drug: cereport; Other Names: labradimil; IND #60315

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Progression Free Survival	A MRI scan will be performed six (6) weeks after completion of radiation, plus at three-month intervals thereafter for two years, as long as there is no evidence of progressive disease. Children who are progression-free two years after treatment will have MRI scanning at six-month intervals, thereafter, for three more years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Roger J. Packer, MD, Children's National Research Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2001
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: May 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 21, 2014
• Last Update Submitted That Met QC Criteria: February 19, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: untreated childhood brain stem glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: ADVL0012; COG-ADVL0012 (Other Identifier: Children's Oncology Group); CCG-ADVL0012 (Other Identifier: Children's Cancer Group); ALK-01-042; CCG-09802 (Other Identifier: Children's Cancer Group); CDR0000067715 (Other Identifier: ClinicalTrials.gov)