Enzastaurin and Temozolomide in Treating Patients With Primary Gliomas

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00516607
First received: August 14, 2007
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: enzastaurin hydrochloride
Drug: temozolomide
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Enzastaurin and Temozolomide in Patients With Gliomas

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Recommended phase II dose [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Pharmacokinetics of enzastaurin hydrochloride alone and in combination with temozolomide [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: July 2007
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00516607

Locations
United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Roy Rampling, MD, PhD University of Glasgow
  More Information

Additional Information:
Publications:
Rampling R, Sanson M, Taal W, et al.: Phase 1 study of LY317615 (enzastaurin) and temozolomide in patients with gliomas - EORTC trial 26054. [Abstract] J Clin Oncol 27 (Suppl 15): A-e13005, 2009.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00516607     History of Changes
Other Study ID Numbers: EORTC-26054, EORTC-26054
Study First Received: August 14, 2007
Last Updated: September 20, 2013
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014