Enzastaurin and Temozolomide in Treating Patients With Primary Gliomas

NCT00516607 | Unknown Phase 1

• 1 other identifier: EORTC-26054
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving enzastaurin together with temozolomide may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin when given together with temozolomide in treating patients with primary gliomas.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent adult brain tumor; adult mixed glioma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult glioblastoma; adult anaplastic ependymoma; adult giant cell glioblastoma; adult gliosarcoma; adult pineal gland astrocytoma

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose

• Dose-limiting toxicity

Secondary Outcomes (4)

• Response rate

• Progression-free survival

• Overall survival

• Pharmacokinetics of enzastaurin hydrochloride alone and in combination with temozolomide

Interventions

enzastaurin hydrochloride DRUG

temozolomide DRUG

pharmacological study OTHER

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed primary supratentorial glioma * WHO histologic grade 3 or 4 * Patients who have undergone prior treatment for low-grade glioma that has transformed to glioblastoma (biopsy proven) allowed * Amenable to standard temozolomide treatment * First or second recurrent disease after prior surgery and/or radiotherapy OR newly diagnosed disease that is not amenable to radiotherapy (e.g., multifocal disease) PATIENT CHARACTERISTICS: * ECOG or WHO performance status 0-2 * Hemoglobin ≥ 10.0 g/dL * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 1.5 x upper limit of normal (ULN) * Alkaline phosphatase and transaminases ≤ 2.5 x ULN * Serum creatinine \< 1.7 mg/dL * Not pregnant or lactating * Negative pregnancy test * Fertile patients must use effective contraception * Clinically normal cardiac function * No ischemic heart disease within the past 6 months * No clinically significant abnormalities or uncontrolled cardiac arrhythmia by ECG * QTc interval ≤ 450 msec (males) or ≤ 470 msec (females) by baseline 12-lead ECG * No history of congenital long QTc syndrome * No history of stroke * No other prior or concurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal or squamous cell skin carcinoma * No unstable systemic diseases * No active uncontrolled infections * No uncontrolled hypertension * No psychological, familial, sociological, or geographical condition that would preclude study participation * Must be able to swallow tablets PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than 1 prior chemotherapy regimen in the adjuvant setting or for first recurrence * Prior temozolomide allowed provided there was no disease progression during temozolomide treatment or within 6 weeks of completing temozolomide treatment * Prior surgery for primary brain tumor within the past 3 months allowed * Patients who are receiving corticosteroid treatment must be on a stable or decreasing dose for at least 1 week before study entry * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) * At least 14 days since prior and no concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following: * Phenytoin * Carbamazepine * Phenobarbital * More than 30 days since prior and no other concurrent investigational treatments * No concurrent anticoagulant treatment (e.g., warfarin) * Low molecular weight heparin for patients who require anticoagulant therapy after starting study treatment may be allowed * No concurrent routine use of colony-stimulating factors * No other concurrent anticancer agents

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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (1)

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Related Publications (1)

• Rampling R, Sanson M, Gorlia T, Lacombe D, Lai C, Gharib M, Taal W, Stoffregen C, Decker R, van den Bent MJ. A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054). Neuro Oncol. 2012 Mar;14(3):344-50. doi: 10.1093/neuonc/nor221. Epub 2012 Jan 29.

  PMID: 22291006 RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms; Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma; Ependymoma; Gliosarcoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roy Rampling, MD, PhD

  University of Glasgow

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2007
• First Posted: August 15, 2007
• Study Start: July 1, 2007
• Primary Completion: November 1, 2008
• Last Updated: February 10, 2015

Record last verified: 2015-02

Locations

GB (1)