Thalidomide and Irinotecan in Treating Patients With Glioblastoma Multiforme Who Have Undergone Radiation Therapy

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Phase II Study Of Thalidomide And CPT-11 (IRINOTECAN) Following Radiotherapy For Glioblastoma Multiforme

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00039468
• Other study ID #: D0134
• Secondary ID: DMS-15615NCI-G02
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2002
• Last updated: October 26, 2011
• Start date: March 2002
• Est. completion date: February 2008

Study information

• Verified date: October 2011
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Thalidomide may stop the growth of glioblastoma multiforme by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with irinotecan may kill any tumor cells remaining after radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of combining thalidomide with irinotecan in treating patients who have glioblastoma multiforme that has been treated with radiation therapy.

Description:

OBJECTIVES:

• Determine the response rate of patients with glioblastoma multiforme treated with thalidomide and irinotecan after radiotherapy.

• Determine the preliminary efficacy of this regimen in these patients.

• Determine the disease-free survival and overall survival of patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

• Assess the quality of life of patients treated with this regimen.

OUTLINE: Beginning 2-4 weeks after completion of radiotherapy, patients receive irinotecan IV over 90 minutes on day 1. Patients also receive oral thalidomide daily. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 1 week after the first course, prior to all subsequent courses, and then after course 6.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: February 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme (GBM)

• Recurrent disease allowed

• Evaluable disease on contrast-enhanced MRI

• Prior external beam radiotherapy required

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• AST or ALT no greater than 5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No significant cardiac disease

• No uncontrolled high blood pressure

• No unstable angina

• No congestive heart failure

• No myocardial infarction within the past 3 months

• No serious cardiac arrhythmias

Gastrointestinal:

• Able to take oral medication

• No gastrointestinal abnormalities

• No requirement for IV alimentation

• No active peptic ulcer disease

Other:

• No active infection

• No serious uncontrolled medical disorder

• No dementia or significantly altered mental status that would preclude study

• No known hypersensitivity to irinotecan or thalidomide

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 forms of effective contraception, including 1 highly effective method, at least 1 month before, during, and for 1 month after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior thalidomide

Chemotherapy:

• No prior irinotecan

• At least 4 weeks since other prior chemotherapy (and demonstrated evidence of disease progression or relapse)

Endocrine therapy:

• Concurrent corticosteroids allowed if on a stable or decreasing dose for at least 1 week prior to study

• No concurrent hormonal therapy for GBM

Radiotherapy:

• See Disease Characteristics

• No concurrent radiotherapy for GBM

Surgery:

• No prior surgical procedures affecting absorption

Other:

• No other concurrent anticancer investigational agents for GBM

• No concurrent cytochrome P450 inhibitors, including the following:

• Nefazodone

• Fluvoxamine

• Fluoxetine

• Sertraline

• Paroxetine

• Venlafaxine

• Ketoconazole

• Itraconazole

• Fluconazole

• Cimetadine

• Clarithromycin

• Diltiazem

• Erythromycin

• Protease inhibitors

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• irinotecan hydrochloride
350 or 700 mg/m2 IV every 3 weeks
• thalidomide
400mg/day oral

Locations

Country	Name	City	State
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Fadul CE, Kingman LS, Meyer LP, Cole BF, Eskey CJ, Rhodes CH, Roberts DW, Newton HB, Pipas JM. A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme. J Neurooncol. 2008 Nov;90(2):229-35. doi: 10.1007/s11060-008-9655-9. Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response	To evaluate the response rate and hence preliminary efficacy of Irinotecan and Thalidomide following radiotherapy in the treatment of newly diagnosed or relapsed glioblastoma multiforme.	2 years	No
Secondary	Toxicity / QOL / Survival	To evaluate 1) toxicity 2) quality of life 3) disease free survival and 4) overall survival of patients treated with this combination.	2 years	Yes