Sirolimus in Treating Patients With Glioblastoma Multiforme

NCT00047073 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000257255UCLA-0203078NCI-G02-2114
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (for phase 1)

  end of phase 1

• Efficacy in terms of progression-free survival at 6 months and objective response (phase II)

  6 months after last subject finishes trial

Secondary Outcomes (2)

• Safety Profile (phase I)

  end of phase I

• Further evaluate safety profile

  end of phase II

Study Arms (2)

Phase 1

EXPERIMENTAL

See intervention description.

Drug: Rapamycin; Procedure: Surgery; Procedure: Supportive Care

Phase 2

EXPERIMENTAL

See intervention description.

Drug: Rapamycin; Procedure: Surgery; Procedure: Supportive Care

Interventions

Rapamycin 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.

Also known as: Sirolimus

Phase 1; Phase 2

Surgery PROCEDURE

Surgical resection.

Phase 1; Phase 2

Supportive Care 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 1; Phase 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Related Publications (1)

• 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.

  PMID: 18215105 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Sirolimus; Surgical Procedures, Operative; Palliative Care

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Timothy F. Cloughesy, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 3, 2002
• First Posted: January 27, 2003
• Study Start: July 1, 2002
• Primary Completion: June 1, 2005
• Study Completion: October 1, 2007
• Last Updated: August 3, 2020

Record last verified: 2012-07

Locations

US (1)