Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

NCT00112736 | Completed Phase 1 Results DMC

• 5 other identifiers: NCI-2012-02921CDR0000429553NABTC04-02NABTC-04-02U01CA062399
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 8

Brief Summary

Erlotinib and temsirolimus and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with erlotinib and to see how well they work in treating patients with recurrent malignant glioma.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (Phase I)

  Oral erlotinab at 150mg constant dose, 3 pts will be treated with temsirolimus IV with escalating doses, starting at 50mg. Doses will increase or decrease based on toxicity observed. 3 pts will be treated at each dose level - 3 dose levels were observed: 50mg, 25mg, and 15mg

  based on first 4 weeks of treatment - cycle 1

• Safety/Dose Limiting Toxities Phase I

  Dose limiting toxities defined as: grade 3 thrombocytopenia, grade 4 anemia and neutropenia, grade \>/= nonhematologic toxicity, and failure to recover from toxicites to be eligible for retreatment in 2 weeks of the last dose of either drug. Also grade 3 nonhematologic toxicities only if they wre refractory to maxiaml medical therapy. MTD defined as dose at which fewer than one-third of patients experienced a DLT Outcome measure defines number of participants who had a defined dose limiting toxicity.

  first 4 weeks of treatment

• Efficacy - Response Phase 1

  pt must have at least 8 weeks of treatment to receive MRI scan, scans are every other cycle (every 2 months). Response measured by a bidimensionally measured leison and clearly defined margins by CT or MRI scan. Complete Response (CR): complete disappearance of all measurable and evaluable disease. No new lesions, not on any steroids Partial Response (PR): \>= 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Steriod dose must be no greater than max used in 1st 8wks of therapy Stable: not qualify for CR, PR, or progression. Steriod dose must be no greater than max used in 1st 8wks of therapy Progression (PD): 25% increase in the sum of products of all measurable lesions over smallest sum observed, OR clear worsening or failure to return for evalution due to death or deteriorating condition (unless clearly unrelated to brain cancer).

  at least 8 weeks of treatment

• Pharmacokinetics (Phase I)

  Tersirolimus Cmax (ng/mL) for cycle 1 is presented in the outcome measure table below for the 3 dose levels blood samples (5ml) was collected in EDTA containing tubes on days 1 and 2 of cycle 1 Collection time points: prior to dosing of both drugs, at end of temsirolimus infusion and at 1,2,4,6, and 24 hr after erlotinib administration

  Days 1, 2 of cycle 1, prior to dosing of both drugs, at end of temsirolimus infusion and at 1,2,4,6, and 24 hr after erlotinib administration

• Progression-free Survival at 6 Months (Phase II)

  Progression (PD): 25% increase in the sum of products of all measurable lesions over smallest sum observed, OR clear worsening or failure to return for evalution due to death or deteriorating condition (unless clearly unrelated to brain cancer). Responses had to be present on 2 consecutive scans and were centrally reviewed.

  Evaluated at baseline and every other cycle, till Month 6

Study Arms (2)

Phase 1 (erlotinib & temsirolimus)

EXPERIMENTAL

PHASE I: Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 (dose escalation). Every 28 days until disease progression or unacceptable toxicity. pharmacological study: Correlative studies

Drug: erlotinib; Drug: temsirolimus; Other: pharmacological study

Phase 2 temsirolimus MTD & erlotinib

EXPERIMENTAL

Oral erlotinib 1 daily days 1-28 (150mg), temsirolimus IV 30 minutes days 1, 8, 15, 22 at MTD phse I. Every 28 days until disease progression or unacceptable toxicity. PHASE II (preoperative component): Patients who are surgical candidates may opt to undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these patients receive oral erlotinib once daily until surgery. Patients also receive temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive temsirolimus at the MTD and erlotinib as in phase I. therapeutic conventional surgery: Undergo surgical resection laboratory biomarker analysis: Correlative studies

Drug: erlotinib; Drug: temsirolimus; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Interventions

erlotinib DRUG

Given orally

Also known as: CP-358,774, erlotinib hydrochloride, OSI-774

Phase 1 (erlotinib & temsirolimus); Phase 2 temsirolimus MTD & erlotinib

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, Torisel

Phase 1 (erlotinib & temsirolimus); Phase 2 temsirolimus MTD & erlotinib

therapeutic conventional surgery PROCEDURE

Undergo surgical resection

Phase 2 temsirolimus MTD & erlotinib

laboratory biomarker analysis OTHER

Correlative studies

Phase 2 temsirolimus MTD & erlotinib

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Phase 1 (erlotinib & temsirolimus)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified (NOS) will be eligible for this protocol; patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must have signed an authorization for the release of their protected health information; patients must be registered in the Adult Brain Tumor Consortium (ABTC) Central Office database prior to treatment with study drug
• Patients must have a life expectancy \> 8 weeks
• Patients must have a Karnofsky performance status of \>= 60
• Patients must have recovered from the toxic effects of prior therapy: 4 weeks (28 days) from any investigational agent, 4 weeks (28 days) from prior cytotoxic therapy, two weeks (14 days) from vincristine, 6 weeks (42 days) from nitrosoureas, 3 weeks (21 days) from procarbazine administration, and 1 week (7 days) for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count); any questions related to the definition of non-cytotoxic agents should be directed to the study chair
• WBC \>= 2,000/ul
• ANC \>= 1,500/mm\^3
• Platelet count of \>= 100,000/mm\^3
• Hemoglobin \>= 10 gm/dl
• Total bilirubin within normal institutional limits
• AST (SGOT)/ALT (SGPT) =\< 2.5 X institutional ULN
• Creatinine \< 1.5 mg/dL
• Patients must have cholesterol level =\< 350 mg/dl and triglycerides level =\< 400 mg/dl
• Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan; a scan should be performed within 14 days prior to registration; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement
• Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 6 weeks (42 days) from the completion of radiation therapy to study entry

You may not qualify if:

• Patients must not be on an enzyme-inducing anti-epileptic drug (EIAED); if previously on an EIAED, the patient must be off of it for at least two weeks prior to registration
• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
• Patients must not have active infection or serious intercurrent medical illness
• Patients must not be pregnant/breast feeding and must agree to practice adequate contraception; women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration; patients must not be pregnant; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
• Patients must not have received prior therapy with CCI-779 (temsirolimus), OSI-774 (erlotinib) or other mTOR or epidermal growth factor receptor inhibitors
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study due to possible retro-viral drug interactions

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (8)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

National Cancer Institute Neuro-Oncology Branch

Bethesda, Maryland, 20814, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Wen PY, Chang SM, Lamborn KR, Kuhn JG, Norden AD, Cloughesy TF, Robins HI, Lieberman FS, Gilbert MR, Mehta MP, Drappatz J, Groves MD, Santagata S, Ligon AH, Yung WK, Wright JJ, Dancey J, Aldape KD, Prados MD, Ligon KL. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014 Apr;16(4):567-78. doi: 10.1093/neuonc/not247. Epub 2014 Jan 26.

  PMID: 24470557 RESULT

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Erlotinib Hydrochloride; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Patrick Y Wen
• Organization: Adult Brain Tumor Consortium (ABTC)

pwen@partners.org

Study Officials

• Patrick Wen, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: April 1, 2005
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2014
• Last Updated: June 15, 2015
• Results First Posted: June 15, 2015

Record last verified: 2015-05

Locations

US (8)