Sirolimus in Treating Patients With Glioblastoma Multiforme

NCT ID: NCT00047073

Last Updated: 2020-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2007-10-31

Brief Summary

RATIONALE: Chemotherapy drugs such as sirolimus use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase I/II trial to study the effectiveness of sirolimus in treating patients who have glioblastoma multiforme that did not respond to previous radiation therapy.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of sirolimus in patients with glioblastoma multiforme.
• Determine the safety profile of this drug in these patients.
• Determine the efficacy of this drug, in terms of 6-month progression-free survival and objective response, in these patients.

OUTLINE: This is a dose-escalation study.

• Phase I: Patients receive oral sirolimus for 5-7 days before surgery. Patients then undergo surgical resection. Patients resume oral sirolimus once daily after full recovery from surgery. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

• Phase II: Patients receive oral sirolimus as in phase I at the dose determined in that phase.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of the study within 3-12 months. A total of 32 patients will be accrued for phase II of the study.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1

See intervention description.

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

Phase 1: Initial dose 6mg on day 1 and then 2mg each day for 5-7 days before surgery. No dosing during surgery recovery. After recorvery 6mg loading dose on day 1 then 2mg each day. Cycle is every 4 weeks.

Dose escalation: Level 2: 15mg load/5mg/day, Level 3: 30mg load/10mg/day, Level 4: 45mg load/15mg/day.

Phase 2: Will utilize dose established in phase I. Dosing schedule will remain the same.

Surgery

Intervention Type: PROCEDURE

Surgical resection.

Supportive Care

Intervention Type: PROCEDURE

Corticosteroids should be used in smallest dose to control symptoms of cerebral edema and mass effect.

Anti-seizure medications should be used as indicated. Febrile neutropenia may be managed according to local institution's infectious disease guidelines.

If neurosurgical management is required for reasons not due to tumor progression, these procedures must be documented.

Phase 2

See intervention description.

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

Phase 1: Initial dose 6mg on day 1 and then 2mg each day for 5-7 days before surgery. No dosing during surgery recovery. After recorvery 6mg loading dose on day 1 then 2mg each day. Cycle is every 4 weeks.

Dose escalation: Level 2: 15mg load/5mg/day, Level 3: 30mg load/10mg/day, Level 4: 45mg load/15mg/day.

Phase 2: Will utilize dose established in phase I. Dosing schedule will remain the same.

Surgery

Intervention Type: PROCEDURE

Surgical resection.

Supportive Care

Intervention Type: PROCEDURE

Corticosteroids should be used in smallest dose to control symptoms of cerebral edema and mass effect.

Anti-seizure medications should be used as indicated. Febrile neutropenia may be managed according to local institution's infectious disease guidelines.

If neurosurgical management is required for reasons not due to tumor progression, these procedures must be documented.

Interventions

Rapamycin

Phase 1: Initial dose 6mg on day 1 and then 2mg each day for 5-7 days before surgery. No dosing during surgery recovery. After recorvery 6mg loading dose on day 1 then 2mg each day. Cycle is every 4 weeks.

Dose escalation: Level 2: 15mg load/5mg/day, Level 3: 30mg load/10mg/day, Level 4: 45mg load/15mg/day.

Phase 2: Will utilize dose established in phase I. Dosing schedule will remain the same.

Intervention Type: DRUG

Surgery

Surgical resection.

Intervention Type: PROCEDURE

Supportive Care

Corticosteroids should be used in smallest dose to control symptoms of cerebral edema and mass effect.

Anti-seizure medications should be used as indicated. Febrile neutropenia may be managed according to local institution's infectious disease guidelines.

If neurosurgical management is required for reasons not due to tumor progression, these procedures must be documented.

Intervention Type: PROCEDURE

Other Intervention Names

Sirolimus

Eligibility Criteria

Inclusion Criteria

• No limits on prior therapy
• Phase II patients:

• Tumor progression by MRI or CT scan required within the past 14 days if recurrent disease is present
• No prior therapy for more than 3 relapses
• Recent resection of recurrent or progressive tumor allowed as long as all of the following conditions apply:

• Recovered from surgery
• MRI or CT scan performed no more than 96 hours since prior surgery OR within 4-6 weeks after surgery
• Baseline MRI or CT scan performed within 14 days of study entry

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT less than 1.5 times ULN

Renal

• Creatinine less than 1.5 mg/dL

Other

• Cholesterol less than 350 mg/dL
• Triglycerides less than 400 mg/dL
• No concurrent disease that would obscure toxicity or dangerously alter drug metabolism
• No other significant uncontrolled serious medical illness that would preclude study participation
• No other cancer except non-melanoma skin cancer or carcinoma in situ of the cervix unless patient is in complete remission and off all therapy for that disease for at least 3 years
• No active infection
• No prior allergic reactions to compounds of similar chemical or biological composition to sirolimus
• No psychiatric illness that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior interferon

Chemotherapy

• At least 2 weeks since prior vincristine
• At least 3 weeks since prior procarbazine
• At least 6 weeks since prior nitrosoureas

Endocrine therapy

• At least 1 week since prior tamoxifen

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy
• At least 1 week since prior noncytotoxic agents (except radiosensitizers)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

UCLA

Principal Investigators

Timothy F. Cloughesy, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Countries

United States

References

Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D, Liau L, Martin N, Becker D, Bergsneider M, Lai A, Green R, Oglesby T, Koleto M, Trent J, Horvath S, Mischel PS, Mellinghoff IK, Sawyers CL. Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 2008 Jan 22;5(1):e8. doi: 10.1371/journal.pmed.0050008.

Reference Type: RESULT

PMID: 18215105 (View on PubMed)

Other Identifiers

UCLA-0203078

Identifier Type: -

Identifier Source: secondary_id

NCI-G02-2114

Identifier Type: -

Identifier Source: secondary_id

CDR0000257255

Identifier Type: -

Identifier Source: org_study_id