Metastatic Cancer
Conditions
Keywords
tumors metastatic to brain
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide and vinorelbine in treating patients who have recurrent brain metastases.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of vinorelbine when administered in combination with temozolomide in patients with recurrent brain metastases (phase I accrual completed). * Determine the safety and feasibility of this treatment regimen in these patients. * Determine the efficacy of this treatment regimen, in terms of objective radiographic response and overall and progression-free survival, in these patients. OUTLINE: This is a dose-escalation study of vinorelbine. Patients receive vinorelbine IV over 5-10 minutes on days 1 and 8 and oral temozolomide once daily on days 1-7 and 15-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 20-35 patients will be treated at that dose level. Patients are followed every 3-4 months. PROJECTED ACCRUAL: A minimum of 3 patients will be accrued for the phase I portion of this study and 20-35 patients will be accrued for the phase II portion of this study within 2 years.
Interventions
DRUGtemozolomide
DRUGvinorelbine tartrate
Sponsors
National Cancer Institute (NCI)
Northwestern Memorial Hospital
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
L: * Age \> or = 18 years. * Karnofsky performance score \> or = 60. * Histopathologic confirmation of the diagnosis of a solid tumor malignancy. The brain metastasis diagnosis per se does not have to be pathologically confirmed if the clinical and neuro radiographic picture is typical. * MRI (or CT if the patient cannot undergo MRI) evidence of evaluable disease in the brain. * Absolute neutrophil count \> or = 1,500/mm³. Platelet count \> or = 100,000/mm³. * Hemoglobin \> or = 10 g/dl. * BUN and serum creatinine both \< 1.5 times upper limit of normal. * Total and direct bilirubin both \< 1.5 times upper limit of normal. * SGOT and SGPT both \< or = 3 times upper limit of normal. * Alkaline phosphatase \< or = 2 times upper limit of normal. * At least two weeks must have elapsed from brain biopsy, craniotomy, or other surgery. * Life expectancy \> or = 8 weeks. * Patient or their legal guardian or legal next-of-kin must provide written informed consent prior to patient's registration on study. * At least four weeks must have elapsed from previous external beam radiation therapy, or eight weeks from stereotactic radiosurgery. * Patients treated with radiosurgery should have evidence of progression at a distant site in the brain, or confirmation of tumor progression by biopsy or PET scan.
Exclusion criteria
* Previous treatment with temozolomide, dacarbazine or vinorelbine. * Patients who have not recovered from all acute toxicities of prior therapies. * Patients with evidence of leptomeningeal metastases or primary dural metastases. * Patients who are poor medical risks because of nonmalignant systemic disease, as well as those with acute infection requiring treatment with intravenous antibiotics. * Patients whose psychiatric condition would, in the judgment of the principal investigator, make it unlikely that they could adhere to the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response Assessed by Macdonald Criteria Every 2 Months | 2 years | All patients will have their tumor measurements recorded at baseline and at the time of each MRI scan. Lesions must be measured in two dimensions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 15mg/m2 - Vinorelbine Temozolomide and 15mg/m2 Vinorelbine for Patients with Recurrent Brain Metastases | 7 |
| 20mg/m2 - Vinorelbine Temozolomide and 20mg/m2 Vinorelbine for Patients with Recurrent Brain Metastases | 4 |
| 25mg/m2 - Vinorelbine Temozolomide and 25mg/m2 Vinorelbine for Patients with Recurrent Brain Metastases | 22 |
| 30mg/m2 - Vinorelbine Temozolomide and 30mg/m2 Vinorelbine for Patients with Recurrent Brain Metastases | 16 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Clinical progression | 0 | 0 | 3 | 0 |
| Overall Study | Patient non-compliance | 1 | 0 | 0 | 0 |
| Overall Study | Patient not treated | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 15mg/m2 - Vinorelbine | 20mg/m2 - Vinorelbine | 25mg/m2 - Vinorelbine | 30mg/m2 - Vinorelbine | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 5 Participants | 6 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 17 Participants | 10 Participants | 34 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 13 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 9 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 4 | 19 / 22 | 16 / 16 |
| serious Total, serious adverse events | 4 / 7 | 4 / 4 | 8 / 22 | 9 / 16 |
Outcome results
Primary
Radiographic Response Assessed by Macdonald Criteria Every 2 Months
All patients will have their tumor measurements recorded at baseline and at the time of each MRI scan. Lesions must be measured in two dimensions.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 15mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Partial Response (PR) | 0 participants |
| 15mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Minor Response (MR) | 0 participants |
| 15mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Complete Response (CR) | 0 participants |
| 15mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Stable Disease (SD) | 3 participants |
| 15mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Progression of Disease (POD) | 2 participants |
| 20mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Minor Response (MR) | 0 participants |
| 20mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Partial Response (PR) | 1 participants |
| 20mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Stable Disease (SD) | 2 participants |
| 20mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Progression of Disease (POD) | 1 participants |
| 20mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Complete Response (CR) | 0 participants |
| 25mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Progression of Disease (POD) | 11 participants |
| 25mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Complete Response (CR) | 0 participants |
| 25mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Minor Response (MR) | 1 participants |
| 25mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Stable Disease (SD) | 4 participants |
| 25mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Partial Response (PR) | 0 participants |
| 30mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Complete Response (CR) | 1 participants |
| 30mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Stable Disease (SD) | 3 participants |
| 30mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Minor Response (MR) | 0 participants |
| 30mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Progression of Disease (POD) | 12 participants |
| 30mg/m2 - Vinorelbine | Radiographic Response Assessed by Macdonald Criteria Every 2 Months | Partial Response (PR) | 0 participants |