Trial Outcomes & Findings for Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer (NCT NCT00080938)

Last Updated: 2023-06-29

Results Overview

Response was assessed per Response Evaluation Criteria in Solid Tumor (RECIST) by brain MRI in the 21 eligible and treated patients.Complete response (CR): complete disappearance of the clinically detectable malignant brain metastasis(es) being followed on MRI scan off corticosteroids and a stable or improving neurologic exam. Partial response (PR): greater than or equal to a 50% reduction in the sum of the product(s) of the maximal cross-sections on MRI scan with a stable or decreasing dose of corticosteroids and a stable or improving neurologic exam. Response = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

assessed every cycle while on treatment, then every 3 months for 2 years

Results posted on

2023-06-29

Participant Flow

Study Activated on 10/18/2005, accrued its first patient on 12/20/2005, terminated on 3/13/2007. Institutes include Mayo Clinic Rochester, Northwestern University, Wisconsin, University of, Stanford University, Lankenau Hospital,Toledo Community Hosp Onc Prog CCOP,Sanford Cancer Ctr-Oncology Clinic,Carle Cancer Center CCOP

Participant milestones

Participant milestones
Measure	Temozolamide and Radiation Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Overall Study STARTED	26
Overall Study Began Protocol Therapy	25
Overall Study Eligible and Treated	21
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Temozolamide and Radiation Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	6
Overall Study Death	2
Overall Study Lack of Efficacy	7
Overall Study other disease	1
Overall Study Not started protocol therapy	1
Overall Study Ineligible	4

Baseline Characteristics

Temozolomide and Radiation Therapy in Treating Patients With Brain Metastasis Secondary to Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temozolamide and Radiation n=21 Participants Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants

PRIMARY outcome

Timeframe: assessed every cycle while on treatment, then every 3 months for 2 years

Population: Eligible and treated patients

Outcome measures

Outcome measures
Measure	Temozolamide and Radiation n=21 Participants Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Number of Patients With Intracranial Response	3 participants

SECONDARY outcome

Timeframe: assessed every 3 months for 2 years

Population: Eligible, treated patients

1-year CNS progression free rate is the percentage of patients who had no CNS progression after being followed for 1 year . Progressive disease (CNS) was defined as a 25% or greater increase in the sum of the product(s) of the maximal cross-sections on MRI scan, reappearance of any lesion that has disappeared, development of any new lesion(s), stable disease with a deterioration of neurologic exam, or clear worsening of any evaluable disease.

Outcome measures

Outcome measures
Measure	Temozolamide and Radiation n=21 Participants Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
1-year Neurologic (Central Nervous System, CNS) Progression Free Rate	90.5 percentage of participants Interval 69.6 to 98.8

SECONDARY outcome

Timeframe: assessed every 3 months for 2 years

Population: Eligible and treated patients

Time to non-CNS progression was calculated from time of protocol entry to time of first systemic progressive disease or death. Patients alive and non-CNS progression-free at last follow-up were censored. Disease progression was defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter (per RECIST criteria). Development of new lesions in non-CNS sites also constituted non-CNS progression. The 21 eligible and treated patients were included in the analysis.

Outcome measures

Outcome measures
Measure	Temozolamide and Radiation n=21 Participants Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Time to Non-CNS (Systemic) Progression	3.2 months Interval 1.3 to 5.7

SECONDARY outcome

Timeframe: assessed every 3 months for 2 years

Population: Eligible and treated patients

Overall survival (months) was calculated from time of protocol entry to time of death from any cause. Patients alive at last follow-up were censored. The 21 eligible and treated patients were included in the analysis.

Outcome measures

Outcome measures
Measure	Temozolamide and Radiation n=21 Participants Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Overall Survival Time	7 months Interval 3.9 to 16.6

Adverse Events

Temozolamide and Radiation

Serious events: 10 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Temozolamide and Radiation n=25 participants at risk Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Blood and lymphatic system disorders Anemia	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Investigations Thrombocytopenia	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
General disorders Fatigue	20.0% 5/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Constipation	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Metabolism and nutrition disorders Dehydration	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Muco/stomatitis by exam,oral cavity	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Nausea	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Vomiting	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Infections and infestations Infection Gr0-2 neut, blood	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Nervous system disorders CNS, hemorrhage	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Metabolism and nutrition disorders Hyperglycemia	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Metabolism and nutrition disorders Hyponatremia	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Musculoskeletal and connective tissue disorders Nonneuropathic lower extr muscle weak	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Psychiatric disorders Confusion	4.0% 1/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Nervous system disorders Dizziness	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment

Other adverse events

Other adverse events
Measure	Temozolamide and Radiation n=25 participants at risk Patients were to receive whole brain radiation therapy (WBRT), 30 Gy in ten fractions, plus Temozolomide (TMZ) given at a dose of 75 mg/m2/day for 14 days starting on day 1 of radiotherapy. Three weeks after completion of WBRT, TMZ was to be given at a dose of 200 mg/m2/day x 5 days (or 150 mg/m2/day if prior chemotherapy) every 28 days for up to 6 cycles post WBRT (for a total of 7 cycles of protocol treatment).
Blood and lymphatic system disorders Anemia	44.0% 11/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Investigations Leukopenia	16.0% 4/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Investigations Thrombocytopenia	32.0% 8/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
General disorders Fatigue	52.0% 13/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Skin and subcutaneous tissue disorders Alopecia	36.0% 9/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Skin and subcutaneous tissue disorders Pruritus/itching	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Skin and subcutaneous tissue disorders Rash/desquamation	12.0% 3/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Injury, poisoning and procedural complications Radiation dermatitis	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Metabolism and nutrition disorders Anorexia	16.0% 4/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Constipation	24.0% 6/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Muco/stomatitis by exam,oral cavity	16.0% 4/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Nausea	32.0% 8/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Taste disturbance	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Gastrointestinal disorders Vomiting	20.0% 5/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Hepatobiliary disorders ALT Increased	24.0% 6/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Hepatobiliary disorders AST Increased	16.0% 4/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Nervous system disorders Neuropathy-sensory	8.0% 2/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment
Nervous system disorders Head/headache	20.0% 5/25 • Assessed every cycle (cycle 1=35 days, All other cycles =28 days) while on treatment and for 30 days after the end of the treatment

Additional Information

Study Statistician

Eastern Cooperative Oncology Group (ECOG) Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place