Enzastaurin and Temozolomide in Treating Patients With Primary Gliomas

February 9, 2015 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Phase I Study of Enzastaurin and Temozolomide in Patients With Gliomas

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Recommended phase II dose
Dose-limiting toxicity

Secondary Outcome Measures

Outcome Measure
Response rate
Progression-free survival
Overall survival
Pharmacokinetics of enzastaurin hydrochloride alone and in combination with temozolomide

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Roy Rampling, MD, PhD, University of Glasgow

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

August 14, 2007

First Submitted That Met QC Criteria

August 14, 2007

First Posted (Estimate)

August 15, 2007

Study Record Updates

Last Update Posted (Estimate)

February 10, 2015

Last Update Submitted That Met QC Criteria

February 9, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-26054

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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