Sirolimus in Treating Patients With Glioblastoma Multiforme

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00047073
First received: October 3, 2002
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: Rapamycin
Procedure: Surgery
Procedure: Supportive Care
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (for phase 1) [ Time Frame: end of phase 1 ] [ Designated as safety issue: Yes ]
  • Efficacy in terms of progression-free survival at 6 months and objective response (phase II) [ Time Frame: 6 months after last subject finishes trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety Profile (phase I) [ Time Frame: end of phase I ] [ Designated as safety issue: Yes ]
  • Further evaluate safety profile [ Time Frame: end of phase II ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: July 2002
Study Completion Date: October 2007
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1
See intervention description.
Drug: 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.

Other Name: Sirolimus
Procedure: Surgery
Surgical resection.
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.

Experimental: Phase 2
See intervention description.
Drug: 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.

Other Name: Sirolimus
Procedure: Surgery
Surgical resection.
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed intracranial glioblastoma multiforme
  • Disease progression by MRI or CT scan

    • Confirmation of true progressive disease (not radiation necrosis) by positron-emission tomography, thallium scanning, MRI, or surgical documentation required if patient received prior interstitial brachytherapy or stereotactic radiosurgery
  • Failed prior radiotherapy
  • Phase I patients:

    • Eligible for salvage surgery
    • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00047073

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Timothy F. Cloughesy, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Timothy Cloughesy, M.D., UCLA
ClinicalTrials.gov Identifier: NCT00047073     History of Changes
Other Study ID Numbers: CDR0000257255, P30CA016042, UCLA-0203078, NCI-G02-2114
Study First Received: October 3, 2002
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014