Dose-Intense Temozolomide in Recurrent Glioblastoma

Phase 2 Study of Dose-Intense Temozolomide in Recurrent Glioblastoma

Temozolomide (Temodar) is an FDA approved medication for the treatment of newly diagnosed glioblastomas. In this study, we will be using temozolomide to treat recurrent glioblastomas. We will be using a different dose and schedule than the FDA approved dose and schedule. The purpose of this study is to determine if patients that have failed standard temozolomide treatment will respond to temozolomide when given at a different dose and schedule (21 days every 28 days).

Study Overview

• Status: Completed
• Conditions: Glioblastoma; Gliosarcoma
• Intervention / Treatment: Drug: Temozolomide

Detailed Description

• Participants will be given a medication-dosing calendar for each treatment cycle. Each treatment cycle lasts 4 weeks (28 days) during which time they will be taking temozolomide orally once a day for the first three weeks.
• At the end of each cycle (day 28, +/- 2 days), the following procedures will be performed: Complete physical examination including a neurological exam; vital signs; a review of current medications and symptoms; blood samples; a pregnancy test for women of child-bearing potential; self-administered quality of life questionnaire; brain MRI or CT scan.
• Participants may continue taking temozolomide until their tumor grows or if they experience unacceptable side effects.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Univsersity
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

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:

• Must provide independent consent or must demonstrate willingness to participate in the study and to adhere to dose and visit schedules.
• 18 years of age or older (of either sex, and of any race)
• Histologic diagnosis of GBM or gliosarcoma with an unequivocal progression by MRI or CT scan
• Must have received standard combined modality therapy as first-line treatment consisting of RT plus concomitant temozolomide followed by adjuvant temozolomide (at least 2 cycles of adjuvant temozolomide)
• Gadolinium MRI or contrast CT scan must be obtained within 14 days prior to registration, and must be on a steroid dose that has been stable for at least 5 days.
• Karnofsky Performance status of 60 or greater
• Life expectancy of at least 8 weeks

• Recovered from the toxic effects of prior therapy, and 21 days must have elapsed since prior treatment with temozolomide

  o If a patient has residual toxicity from any previous treatment, toxicity must be ≤ Grade 1

• Laboratory tests within parameters outlined in the protocol
• Female subjects of childbearing potential & male subjects with female partner of childbearing potential must agree to use a medically accepted method of contraception or be surgically sterilized prior to Screening, while receiving protocol-specified medication, and for 30 days after stopping the study medication
• Negative pregnancy test within 48 hours prior to dosing with the study drug (for female subjects of childbearing potential)
• Free of any clinically relevant disease that would, in the Principal Investigator's opinion, interfere with the conduct of the study or study evaluations
• Must be able to adhere to the dosing and visit schedules, and agree to record medication times, concomitant medications, and adverse events (AEs) accurately and consistently in a daily diary
• Unstained slides (at least 15 of 10 micron thickness, or 20 when < 10 micron thickness)or 1 tissue block must be available from the original diagnostic biopsy/surgery or from the biopsy/surgery recurrence
• Participants who have undergone recent resection of recurrent or progressive tumor will be eligible provided at least 2 weeks has elapsed since surgery, and subjects have recovered from surgical-related trauma
• Residual disease following resection of recurrent GBM or gliosarcoma is not mandated for eligibility into the study.

Exclusion Criteria:

• Participant has received a dosing schedule of temozolomide other than 75 mg/m2/day for 42 days during RT followed by adjuvant temozolomide at a dose of 150-200 mg/m2/day for 5 days of a 28-day schedule (standard dose adjustments for toxicity are allowed)
• Any other anti-tumor agent other than standard surgical resection, RT and temozolomide prior to enrollment or during the study period
• Received treatment with BCNU (Gliadel) wafers or GliaSite
• Progressed prior to receiving at least 2 cycles of adjuvant temozolomide
• Pregnant or intending to become pregnant during the study
• In a situation or condition that, in the opinion of the Investigator, may interfere with optimal participation in the study
• Participating in any other clinical study in which an investigational drug is prescribed
• Allergic to or has sensitivity to the study drug or its excipients
• History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless he/she is in complete remission and has not received treatment for that particular disease for the past 3 or more years

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: Single-Arm Study	Drug: Temozolomide; Taken orally daily for the first three weeks of a four-week cycle.; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Month Progression Free Survival	Progression is defined using Modified Macdonald Criteria , using a >/= 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		From patient registration until end of study, assessed up to 54 months
Radiographic Response	Responders on study are those with a best response of either CR or PR. Per Modified Macdonald Criteria for lesions assessed by MRI/CT: Complete Response (CR) = Complete disappearance of all measurable and evaluable disease, no new lesions, no evidence of non-evaluable disease, with no steroids. Partial Response (PR) >/= 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions, no progression of evaluable disease, no new lesions, with steroid dose @ time of response </= max dose w/in the first 8 weeks of therapy.	From patient registration until end of study, assessed up to 54 months
Time to Progression.	Progression is defined using Modified Macdonald Criteria , using a >/= 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).	From patient registration until end of study, assessed up to 54 months

Collaborators and Investigators

• Sponsor: Patrick Y. Wen, MD
• Collaborators: Massachusetts General Hospital; University of Pennsylvania; Brigham and Women's Hospital; Wake Forest University Health Sciences; Dartmouth-Hitchcock Medical Center; Tufts Medical Center; Schering-Plough

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: April 8, 2008
• First Submitted That Met QC Criteria: April 8, 2008
• First Posted (Estimate): April 14, 2008

Study Record Updates

• Last Update Posted (Estimate): March 14, 2014
• Last Update Submitted That Met QC Criteria: February 13, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: recurrent glioblastoma; temozolomide; temodar
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: 08-013; P05516 (Other Identifier: Schering Plough)