Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
temozolomide, radiotherapy
Brief summary
This is a phase II, randomized, multicenter, open-label study designed to assess the safety and tolerability of concomitant chemotherapy with low-dose temozolomide during whole brain radiation and later on at 14 days on/14 days off schedule in patients with cerebral metastases from non-small cell lung cancer (NSCLC). The response to temozolomide will be evaluated by clinical follow up and Magnetic Resonance Imaging (MRI) performed every 2 months. Progression-free survival at 6 months, duration of overall survival, and quality of life will also be evaluated.
Interventions
DRUGTemozolomide and radiotherapy
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100 mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
PROCEDUREWhole brain radiotherapy
2 regimens are allowed: a) 20 fractions of 2 Gray each, administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
Sponsors
AESCA Pharma GmbH
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prior histologic confirmation of non-small cell lung cancer (NSCLC). * Optional: NSCLC histologic confirmation of metastasis of NSCLC. * Presence of unidimensionally measurable disease in the brain. * No previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin. * Age: \>18 years. * Subjects must not have systemic disease that in the opinion of the investigator is in immediate need of chemotherapy * Karnofsky Performance status \>=70%. * Absolute neutrophil count (ANC) \>1,500/mm\^3, platelets \>100,000/mm\^3, hemoglobin \>8 g/dL. * Serum creatinine and bilirubin \<1.5 times upper normal limit of testing laboratory. * Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) \<3 times upper limit of testing laboratory. * Palliative radiation therapy to thorax and bone or other organs (except brain) is acceptable. * Prior neurosurgery \>2 weeks from initiating treatment with temozolomide. * Cortisone medication stable or decreasing within 2 weeks prior to initiating treatment with temozolomide. * Patient is not pregnant or nursing and is advised and willing to use an effective method of contraception. * Written informed consent.
Exclusion criteria
* Chemotherapy or biologic therapy within four weeks prior to initiating therapy with temozolomide. * Prior radiation therapy for brain \<4 weeks from initiating therapy with temozolomide. * Surgery within two weeks prior to temozolomide administration. * Recursive Partitioning Analysis (RPA) class III * Patients with a single brain metastasis amenable to radiosurgery of resection * Known Human Immunodeficiency Virus (HIV) disease. * Acute infection requiring intravenous antibiotics. * Any reason making compliance to the protocol improbable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival (6 Month) | 6 months | The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as \<25% increase in tumor size on CT or MRI. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy With Temozolomide and Radiotherapy Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2). | 22 |
| Radiotherapy Alone 2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12. | 13 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Death | 5 | 4 |
| Overall Study | Discontinued before starting study drug | 4 | 0 |
| Overall Study | Disease Progression | 9 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Chemotherapy With Temozolomide and Radiotherapy | Radiotherapy Alone | Total |
|---|---|---|---|
| Age, Continuous | 65.12 years STANDARD_DEVIATION 12.72 | 63.02 years STANDARD_DEVIATION 8.76 | 64.3 years STANDARD_DEVIATION 11.3 |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 18 | 8 / 13 |
| serious Total, serious adverse events | 8 / 18 | 4 / 13 |
Outcome results
Primary
Number of Participants With Progression-free Survival (6 Month)
The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as \<25% increase in tumor size on CT or MRI.
Time frame: 6 months
Population: Intent to treat (ITT) population (31 of the 35 patients enrolled; 4 participants discontinued prior to start of treatment) was analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy With Temozolomide and Radiotherapy | Number of Participants With Progression-free Survival (6 Month) | 8 Participants |
| Radiotherapy Alone | Number of Participants With Progression-free Survival (6 Month) | 8 Participants |