Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases (RAD0102)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Integrated Therapeutics Group
Information provided by (Responsible Party):
John Fiveash, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00582075
First received: December 20, 2007
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

The protocol is designed to determine the efficacy of temozolomide in preventing the development of new brain metastases within the first year in patients undergoing stereotactic radiation for newly diagnosed brain metastases.


Condition Intervention Phase
Cancer
Brain Metastases
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 II Study of Gamma Knife Radiosurgery and Temozolomide (Temodar) for Newly Diagnosed Brain Metastases

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • To determine the efficacy of temozolomide in preventing the development of new brain metastases within the first year in patients undergoing stereotactic radiation for newly diagnosed brain metastases [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival, toxicity, and quality of life [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: July 2002
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: temozolomide
    TMZ 200mg/m2 days 1-5 repeat q28 days. Patients who have received prior chemotherapy will receive 150 mg/m2 days 1-5
    Other Name: Temodar
Detailed Description:

This is a phase II study. The primary endpoint is the proportion of patients with newly developed metastases who develop new brain metastases within the first year of undergoing stereotactic radiation combined with the administration of temozolamide within the first year post treatment. Retrospective and prospective studies suggest that 50- 60% of long-term survivors develop new brain metastases. Since it is important to observe all patients recruited for a minimum of a year to measure the primary outcome, traditional phase 2 designs such as Simon's two stage optimal design or the mini-max design are not practical in this case. Survival and QOL are secondary end points. QOL will be measured using the Functional Assessment of Cancer Therapy (FACT -BR). It will be administered at baseline, at week four and every three months for 24 months.

This protocol includes radiosurgery with standard radiation doses (15-24 Gy based upon RTOG 9005). Patient may be registered after radiosurgery as long as Temodar is started within two weeks of radiosurgery.

Beginning within two weeks after radiosurgery: TMZ 200mg/m2 days 1-5 repeat q28 days. Patients who have received prior chemotherapy will receive 150 mg/m2 days 1-5.

Temozolomide is continued until there is disease progression defined by systemic progression or new metastases. If lesion treated with radiosurgery progresses in the absence of new CNS tumors or systemic progression, then TMZ will continue. Temozolomide is discontinued for systemic progression requiring other systemic chemotherapy.

Palliative radiation may be administered to non-CNS sites during protocol treatment, but additional systemic chemotherapy will not be administered until patients progress systemically or until new metastases develop.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All subjects must have history of histologically confirmed malignancy. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician.
  • Newly diagnosed brain metastases (four or fewer by thin slice post-contrast MRI).
  • ECOG performance status of less than or equal to 2 for patients with no prior chemotherapy, and less than or equal to 1 for patients with prior chemotherapy.
  • Age greater than 18
  • Life expectancy greater than 12 weeks
  • Subjects given written informed consent
  • Adequate hematologic, renal and liver function as demonstrated by laboratory values performed within 14 days, inclusive, prior to administration of study drug:

    • Absolute neutrophil count (ANC) >= 1500/mm3
    • Platelet count >= 100,000/mm3
    • Hemoglobin >= 9 g/dL
    • BUN and serum creatinine <= 1.5 times upper limit of laboratory normal
    • Total and direct bilirubin <= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, total and direct bilirubin <=5 times upper limit of normal
    • SGOT and SGPT <= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, SGOT and SGPT <=5 times upper limit of normal
    • Alkaline phosphatase <= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, alkaline phosphatase of <= 5 times upper limit of normal

Exclusion Criteria:

  • Patients with small cell lung cancer and lymphoma are ineligible.
  • More than four metastases by thin slice MRI. Note that if a diagnostic study prior to radiosurgery demonstrates only four tumors but the gamma knife treatment-planning scan reveals greater than four tumors, the patients will still be eligible for the protocol if all tumors can be treated with radiosurgery.
  • Chemotherapy within four weeks prior to study drug administration
  • Patients, who in the opinion of the treating medical oncologist, require immediate cytotoxic chemotherapy other than the study drug. Allowed medications include antihormonal agents (i.e., Tamoxifen), herceptin and bisphosphonates.
  • Radiation therapy to greater than or equal to 50% of the bone marrow. Completion of radiation therapy less than 4 weeks prior to study drug administration for radiotherapy to >= 15% of bone marrow and less than 2 weeks prior for radiotherapy to < 15% of bone marrow.
  • Insufficient recovery from all active toxicities of prior therapies
  • Subjects who are poor medical risks because of non-malignant systemic disease
  • Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
  • Previous or concurrent malignancies at other sites, or treatment for malignancy at the site within 5 years of study start with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.
  • Known HIV positively or AIDS-related illness.
  • Pregnant or nursing women.
  • Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.
  • Men who are not advised to use an effective method of contraception.
  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: NCT00582075

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
University of Alabama at Birmingham
Integrated Therapeutics Group
Investigators
Principal Investigator: John Fiveash, M.D. University of Alabama at Birmingham
  More Information

Publications:
Abrey JD, Olson DY, Boutros M, Mack A, Rodavitch JJ, Raizer MG. A Phase II Study of Temozolomide for Recurrent Brain Metastases. Malkin; Memorial Sloan-Kettering Cancer Center, New York, NY. Abstract 643
Patel M, McCully C, Godwin K, Balis F: Plasma and cerebrospinal fluid pharmacokinetics of temozolomide. Proc. ASCO. 1995; 14:1485
O'Reilly SM, Newlands ES, Stevens MFG, Brampton MH, Slack JA et al: Temozolomide (CCRG 81045; M&B 39831; NSC 362856): a new oral cytotoxic agent with activity against melanoma, mycosis fungoides and high-grade glioma. Proc. AACR. 1992; 33: A1267
O'Reilly SM, Newlands ES, Glaser MG et al: Temozolomide: a new oral cytotoxic agent with promising activity against gliomas. Proc. ASCO. 1993; 12:499
Brada M, Moore S, Judson I, Batra VJ, Quartey P, Dugan M: A Phase I study of SCH 52365 (temozolomide) in adult patients with advanced cancer. Proc. ASCO. 1995; 14:1521
Yung A, Levin VA, Albright R, Olson J, Fredericks R, Fink K, Prados M, Brada M, Spence A, Brunner J, Yue N, Dugan MH, Zaknoen S. Temodal Brain Tumor Group: Randomized trial of temodal (TEM) vs. procarbazine (PCB) in glioblastoma multi-forme (GBM) at first relapse [abstract]. Proceedings of the American Society of Clinical Oncology. 1999; 18:139a.
Cristododoulou C, Bafaloukos D, Kosmidis P, Samantas E, Bamias A, Papakostas P, Karabelis A, Bacoyiannis C, Skarlos D. Phase II study of Temozolomide in heavily pretreated patients with brain metastases from solid tumors. Hellenic Co-operative Oncology Group, Athens, Greece.

Responsible Party: John Fiveash, MD, Professor and Vice Chair, University of Alabama at Birmingham Department of Radiation Oncology, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00582075     History of Changes
Other Study ID Numbers: F020522015
Study First Received: December 20, 2007
Last Updated: February 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Cancer
Brain metastases
Gamma Knife Radiosurgery
Temodar
Temozolomide

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Nervous System Diseases
Nervous System Neoplasms
Pathologic Processes
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014