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

Cancer Clinical Trial

— RAD0102  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00582075
• Other study ID #: F020522015
• Status: Completed
• Phase: Phase 2
• Start date: July 2002
• Est. completion date: June 2015

Study information

• Verified date: March 2023
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2015
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Cancer
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Integrated Therapeutics Group

Country where clinical trial is conducted

United States, 

References & Publications (42)

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

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Data on file at the Cancer Research Campaign Data Center. Phase II trial of temozolomide in high-grade glioma. Schering-Plough Research Institute. Study No. H93-090-50).

Data on file at the Cancer Research Campaign Data Center. Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma. Schering-Plough Research Institute. Study No. H93-089-50).

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O'Reilly SM, Newlands ES, Glaser MG, Brampton M, Rice-Edwards JM, Illingworth RD, Richards PG, Kennard C, Colquhoun IR, Lewis P, et al. Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur J Cancer. 1993;29A(7):940-2. doi: 10.1016/s0959-8049(05)80198-4. Erratum In: Eur J Cancer 1993;29A(10):1500. — View Citation

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

Paraskevaidis E, Antonadou D, Sarris G, Kolliarakis N, Economou I, Karageirgus P, Throuvalas N. A Phase II randomized trial of synchronous radiotherapy with temozolomide in brain metastases. Metaxas Cancer Hospital, Pireus, Greece

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SN92131: Single-Cycle Oral Toxicity Study of SCH 52365 in Rats. Schering Plough Research Institute.

SN92132: Single-Cycle Oral Toxicity Study of SCH 52365 in Dogs. Schering-Plough Research Institute

SN92133: Three-Cycle Oral Toxicity Study of SCH 52365 in Rats. Schering Plough Research Institute.

SN92134: Three-Cycle Oral Toxicity Study of SCH 52365 in Dogs. Schering-Plough Research Institute

SN92380: SCH 52365: Mass Balance and Excretion of 14C-SCH 52365 Following a Single Intravenous or Oral Dose in Male Rats. Schering-Plough Research Institute

SN92381: SCH 52365: Absorption, Metabolism, Excretion, and Pharmacokinetics of 14C-SCH 52365 Following a Single Oral or Intravenous Dose in the Male Rat. Schering-Plough Research Institute

SN92382: SCH 52365: Absorption, Metabolism, Excretion, and Pharmacokinetics of 14C-SCH 52365 Following a Single Oral And Intravenous Dose in the Male Dog. Schering-Plough Research Institute

SN92383: SCH 52365: Absorption, Distribution and Metabolism of 14C SCH 52365 Following a Single Oral Dose in Male Rats. Schering-Plough Research Institute

SN92384: SCH 52365: Pharmacokinetics of SCH 52365 in Rats Following a Single Oral Gavage or Intravenous Dose. Schering-Plough Research Institute

SN92385: SCH 52365: Pharmacokinetics of SCH 52365 in Beagle Dogs Following a Single Oral Gavage or a Single Intravenous Cross-Over Study. Schering Plough Research Institute

SN93092: Single-Cycle Oral Toxicity Study with Lower Doses of SCH 52365 in Rats. Schering-Plough Research Institute

SN93093: Single-Cycle Oral Toxicity Study with Lower Doses of SCH 52365 in Dogs. Schering-Plough Research Institute

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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.

* Note: There are 42 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Distant Brain Failure (DBF) at One Year	Patients developing distant brain failure (DBF) at one year. An approximation method was used to arrive at the reported percentage.	1 years
Secondary	Overall Survival		2 years