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A Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors

Primary Purpose

Brain Neoplasms, Glioma, Medulloblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RMP-7 and carboplatin
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Neoplasms focused on measuring Blood-Brain Barrier, Bradykinin, Children, Glioma, Medulloblastoma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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/CURRENT THERAPY: See Disease Characteristics At least 6 months since carboplatin. At least 3 weeks since myelosuppressive therapy. Patients who received stem cell or bone marrow rescue after nitrosourea therapy are eligible after 3 weeks if they have recovered from hematologic toxicities of their prior therapy. Concurrent steroids allowed if dose stable for at least 2 weeks prior to entry. Recovered from toxic effects of any prior therapy. PATIENT CHARACTERISTICS: Age: 21 and under. Performance status: ECOG 0-2. Life expectancy: At least 8 weeks. HEMATOLOGIC: Absolute granulocyte count greater than 1,500/mm(3). Platelet count greater than 100,000/mm(3) (at least 75,000/mm(3) 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.

Sites / Locations

  • National Cancer Institute (NCI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001502
Brief Title
A Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors
Official Title
Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2000
Overall Recruitment Status
Completed
Study Start Date
April 1996 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
The presence of a highly selective blood-brain barrier (BBB) at the level of the brain capillary endothelium prevents chemotherapeutic agents from attaining therapeutic concentrations at the target site. RMP-7 is a synthetic bradykinin analog which specifically binds to B2 receptors expressed on the brain capillary endothelial cells and preferentially increases capillary permeability within CNS tumors. Carboplatin is an anticancer agent with preclinical and clinical antitumor activity against a variety of brain tumors. A pediatric phase I trial of the combination of RMP-7 and carboplatin will be conducted to determine the maximum tolerated dose of RMP-7 in children with refractory brain tumors.
Detailed Description
The presence of a highly selective blood-brain barrier (BBB) at the level of the brain capillary endothelium prevents chemotherapeutic agents from attaining therapeutic concentrations at the target site. RMP-7 is a synthetic bradykinin analog which specifically binds to B2 receptors expressed on the brain capillary endothelial cells and preferentially increases capillary permeability within CNS tumors. Carboplatin is an anticancer agent with preclinical and clinical antitumor activity against a variety of brain tumors. A pediatric phase I trial of the combination of RMP-7 and carboplatin will be conducted to determine the maximum tolerated dose of RMP-7 in children with refractory brain tumors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Neoplasms, Glioma, Medulloblastoma
Keywords
Blood-Brain Barrier, Bradykinin, Children, Glioma, Medulloblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
RMP-7 and carboplatin

10. Eligibility

Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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/CURRENT THERAPY: See Disease Characteristics At least 6 months since carboplatin. At least 3 weeks since myelosuppressive therapy. Patients who received stem cell or bone marrow rescue after nitrosourea therapy are eligible after 3 weeks if they have recovered from hematologic toxicities of their prior therapy. Concurrent steroids allowed if dose stable for at least 2 weeks prior to entry. Recovered from toxic effects of any prior therapy. PATIENT CHARACTERISTICS: Age: 21 and under. Performance status: ECOG 0-2. Life expectancy: At least 8 weeks. HEMATOLOGIC: Absolute granulocyte count greater than 1,500/mm(3). Platelet count greater than 100,000/mm(3) (at least 75,000/mm(3) 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.
Facility Information:
Facility Name
National Cancer Institute (NCI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8187947
Citation
Clements JA. The human kallikrein gene family: a diversity of expression and function. Mol Cell Endocrinol. 1994 Feb;99(1):C1-6. doi: 10.1016/0303-7207(94)90138-4. No abstract available.
Results Reference
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PubMed Identifier
7870689
Citation
Straub JA, Akiyama A, Parmar P. In vitro plasma metabolism of RMP-7. Pharm Res. 1994 Nov;11(11):1673-6. doi: 10.1023/a:1018986510570. No abstract available.
Results Reference
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PubMed Identifier
7931623
Citation
Inamura T, Nomura T, Bartus RT, Black KL. Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumors. J Neurosurg. 1994 Nov;81(5):752-8. doi: 10.3171/jns.1994.81.5.0752.
Results Reference
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A Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors

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