Ph I Oral Topotecan and Temozolomide for Patients With Malignant Gliomas

Glioblastoma Clinical Trial

Official title:

Phase I Trial of Oral Topotecan Plus Temodar in the Treatment of Patients With Malignant Gliomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00610571
• Other study ID #: Pro00003970
• Secondary ID: 5487
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2008
• Last updated: October 23, 2013
• Start date: April 2004
• Est. completion date: April 2012

Study information

• Verified date: October 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Objectives:

• To determine the maximum tolerated dose of oral topotecan when administered with Temodar to patients with malignant glioma

• To characterize any toxicity associated with the combination oral topotecan and Temodar.

• To observe patients for clinical antitumor response when treated with oral topotecan and Temodar.

Description:

Subjects are patients with glioblastoma (GBM), anaplastic astrocytoma (AA) or grade 3 or greater WHO astrocytic, oligodendroglial or mixed glial tumors, which were initially diagnosed by histologic examination of biopsy/resection. Modified classical "3+3" phase I design used to determine maximum tolerated dose of topotecan in combination with Temodar.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: April 2012
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histology: GBM, AA or grade 3 or greater WHO astrocytic, oligodendroglial or mixed glial tumors which were initially diagnosed by histologic exam of biopsy/resection

• Age: > or equal to 18 years

• Performance Status: Karnofsky Performance Status > or equal to 60% at study entry.

• Renal Function: Serum creatinine < 1.5 mg/dl or creatinine clearance > 60 ml/dL.

• Hematologic Status: The following baseline studies will be required before entry:

total granulocyte count > or equal to 1000/microliter; platelet count > 100,000/microliter

• Hepatic Function: Serum SGOT & total bilirubin < or equal to 2.5 times ULN.

• Note: All lab parameters must have been obtained within 1 week of registration

• Consent: Signed informed consent, approved by IRB, will be obtained prior to initiating treatment

• Corticosteroids: For patients currently on corticosteroids, patients should be on stable dose for 1 week prior to study entry, if clinically possible.

• Prior Therapy: Interval of at least 2 weeks between prior surgical resection or prior radiotherapy (XRT) or 1 week from completion of chemotherapy and all toxicities are < or equal to grade 1 & enrollment on this protocol unless there is unequivocal evidence of progressive disease.

• Patients with Reproductive Potential: Patients must agree to practice effective birth control measures while on study and for 2 months after completing therapy

Exclusion Criteria:

• Pregnant or breast feeding women or women or men with reproductive potential not practicing adequate contraception. This therapy may be associated with potential toxicity to the fetus or child that exceeds minimum risks necessary to meet health needs of mother

• Active infection requiring intravenous antibiotics

• Prior failure with either topotecan or temozolomide

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Astrocytoma
• Glioblastoma
• Gliosarcoma

Intervention

Drug:
• Oral Topotecan and Temodar
Temozolomide is taken by mouth once day, every day for 5 consecutive days at dose of 200 mg/m2/day. Oral Topotecan will be taken daily for 5 consecutive days beginning 12-24 hrs after 1st dose of Temozolomide. Dose escalation of Oral Topotecan will be carried out in cohorts of 3 new subjects beginning w dose level 1 @ 0.75 mg/m2/dose.

Locations

Country	Name	City	State
United States	Duke University Health System	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Katy Peters	GlaxoSmithKline, Schering-Plough

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose		6 months	No
Secondary	Safety & efficacy		6 months	Yes

External Links

•   The Preston Robert Tisch Brain Tumor Center at DUKE