Dose-Intense Temozolomide in Recurrent Glioblastoma

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
University of Pennsylvania
Wake Forest School of Medicine
Tufts Medical Center
Dartmouth-Hitchcock Medical Center
Schering-Plough
Information provided by (Responsible Party):
Patrick Y. Wen, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00657267
First received: April 8, 2008
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Glioblastoma
Gliosarcoma
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Dose-Intense Temozolomide in Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 6 Month Progression Free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From patient registration until end of study, assessed up to 54 months ] [ Designated as safety issue: No ]
  • Radiographic Response [ Time Frame: From patient registration until end of study, assessed up to 54 months ] [ Designated as safety issue: No ]
    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.

  • Time to Progression. [ Time Frame: From patient registration until end of study, assessed up to 54 months ] [ Designated as safety issue: No ]
    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).


Enrollment: 58
Study Start Date: May 2008
Study Completion Date: October 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-Arm Study Drug: Temozolomide
Taken orally daily for the first three weeks of a four-week cycle.
Other Name: Temodar

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.
  Eligibility

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

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
  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: NCT00657267

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, North Carolina
Wake Forest Univsersity
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Patrick Y. Wen, MD
Brigham and Women's Hospital
Massachusetts General Hospital
University of Pennsylvania
Wake Forest School of Medicine
Tufts Medical Center
Dartmouth-Hitchcock Medical Center
Schering-Plough
Investigators
Principal Investigator: Patrick Wen, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Patrick Y. Wen, MD, Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00657267     History of Changes
Other Study ID Numbers: 08-013, P05516
Study First Received: April 8, 2008
Results First Received: June 16, 2013
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
recurrent glioblastoma
temodar
temozolomide

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

ClinicalTrials.gov processed this record on September 18, 2014