Dose-Intense Temozolomide in Recurrent Glioblastoma

• ClinicalTrials.gov Identifier: NCT00657267
• Recruitment Status: Completed
• First Posted: April 14, 2008
• Results First Posted: March 14, 2014
• Last Update Posted: March 14, 2014
• Sponsor: Patrick Y. Wen, MD
• Collaborators: Brigham and Women's Hospital; Massachusetts General Hospital; University of Pennsylvania; Wake Forest University Health Sciences; Tufts Medical Center; Dartmouth-Hitchcock Medical Center; Schering-Plough
• Information provided by (Responsible Party): Patrick Y. Wen, MD, Dana-Farber Cancer Institute

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Glioblastoma; Gliosarcoma	Drug: Temozolomide	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Dose-Intense Temozolomide in Recurrent Glioblastoma
• Study Start Date: May 2008
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: October 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 6 Month Progression Free Survival [ Time Frame: 6 months ]
   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 :

1. Overall Survival [ Time Frame: From patient registration until end of study, assessed up to 54 months ]
2. Radiographic Response [ Time Frame: From patient registration until end of study, assessed up to 54 months ]
   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.
3. Time to Progression. [ Time Frame: From patient registration until end of study, assessed up to 54 months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Massachusetts

Tufts Medical Center

Boston, Massachusetts, United States, 02111

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

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 University Health Sciences

Tufts Medical Center

Dartmouth-Hitchcock Medical Center

Schering-Plough

Investigators

• Principal Investigator: Patrick Wen, MD; Dana-Farber Cancer Institute

More Information

• Responsible Party: Patrick Y. Wen, MD, Director, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00657267
• Other Study ID Numbers: 08-013; P05516 ( Other Identifier: Schering Plough )
• First Posted: April 14, 2008
• Results First Posted: March 14, 2014
• Last Update Posted: March 14, 2014
• Last Verified: February 2014

Keywords provided by Patrick Y. Wen, MD, 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; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents