Enzastaurin and Temozolomide in Treating Patients With Primary Gliomas

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase I Study of Enzastaurin and Temozolomide in Patients With Gliomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00516607
• Other study ID #: EORTC-26054
• Secondary ID: EORTC-26054
• Status: Active, not recruiting
• Phase: Phase 1
• First received: August 14, 2007
• Last updated: February 9, 2015
• Start date: July 2007

Study information

• Verified date: February 2015
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

• To assess if full doses of enzastaurin hydrochloride and temozolomide can be used in combination for the treatment of patients with primary gliomas.

• To determine the recommended phase II dose.

OUTLINE: This is a multicenter study.

Patients receive oral enzastaurin hydrochloride once or twice daily on days 1-28* and oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *During the first course only, patients also receive enzastaurin hydrochloride on day -1.

Patients undergo blood sample collection on day 22 of course 1 and on day 5 of course 2 for pharmacokinetic studies of enzastaurin hydrochloride.

After completion of study treatment, patients are followed within 30 days and then every 3 months thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 28
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• enzastaurin hydrochloride

• temozolomide

Other:
• pharmacological study

Locations

Country	Name	City	State
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Country where clinical trial is conducted

United Kingdom, 

References & 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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose			Yes
Primary	Dose-limiting toxicity			Yes
Secondary	Response rate			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Pharmacokinetics of enzastaurin hydrochloride alone and in combination with temozolomide			No