Ph I Oral Topotecan and Temozolomide for Patients With Malignant Gliomas

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

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.

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma
• Intervention / Treatment: Drug: Oral Topotecan and Temodar

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Oral Topotecan and Temodar; Two separate strata to accrue independently. Stratum 1: Patients taking receiving Dilantin, Tegretol, Trileptal or Phenobarbital. Stratum 2: Patients on anti-convulsants other than Dilantin, Tegretol, Trileptal or Phenobarbital or patients not on any anti-convulsants

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.; Other Names: Temodar - Temozolomide; Topotecan - Hycamtin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
maximum tolerated dose	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety & efficacy	6 months

Collaborators and Investigators

• Sponsor: Katy Peters
• Collaborators: GlaxoSmithKline; Schering-Plough

Publications and helpful links

Helpful Links

• The Preston Robert Tisch Brain Tumor Center at Duke

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: January 28, 2008
• First Submitted That Met QC Criteria: February 7, 2008
• First Posted (Estimate): February 8, 2008

Study Record Updates

• Last Update Posted (Estimate): October 25, 2013
• Last Update Submitted That Met QC Criteria: October 23, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Temozolomide; GBM; Temodar; Topotecan; Hycamtin; Malignant Gliomas; Brain tumor; Anaplastic astrocytoma; AA; Glioblastoma Multiform; Gliosarcoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Astrocytoma; Gliosarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Temozolomide; Topotecan
• Other Study ID Numbers: Pro00003970; 5487 (Old Duke IRB number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No