Brain Tumor, Central Nervous System Tumor
Conditions
Keywords
untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma, childhood spinal cord neoplasm, childhood oligodendroglioma, childhood low-grade cerebral astrocytoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, vincristine, and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: This pilot study is studying giving carboplatin and vincristine together with temozolomide in treating children with progressive and/or symptomatic low-grade glioma.
Detailed description
OBJECTIVES: Primary * Determine the feasibility and toxicity of an induction and maintenance regimen comprising carboplatin, vincristine, and temozolomide in children with progressive and/or symptomatic low-grade gliomas. Secondary * Determine response rate in patients treated with this regimen. * Determine 3-year progression-free survival and overall survival of patients treated with this regimen. * Correlate response and progression-free survival with the genomic profile of tumors in patients treated with this regimen. OUTLINE: This is a pilot study. * Induction therapy: Patients receive carboplatin IV over 1 hour on days 1, 8, 15, and 22; vincristine IV on days 1, 8, 15, 22, 29, and 36; and oral temozolomide on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. * Maintenance therapy: Patients receive carboplatin and temozolomide as in induction therapy and vincristine IV on days 1, 8, and 15. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 2 years.
Interventions
DRUGcarboplatin
Given IV
DRUGtemozolomide
Given orally
DRUGvincristine sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed progressive and/or symptomatic low-grade glioma, including any of the following: * WHO grade I or II astrocytoma * Grade I or II oligodendrogliomas * Mixed oligodendrogliomas * Gangliogliomas * Measurable disease * Progressive and/or symptomatic supratentorial or spinal cord tumors that cannot be removed for anatomical reasons are allowed * Optic pathway tumors allowed provided there is evidence of progressive disease by MRI and/or symptoms of deteriorating vision, progressive hypothalamic/pituitary dysfunction, or diencephalic syndrome * Dorsally exophytic brainstem gliomas that were previously resected more than 50% are allowed provided the residual tumor shows progression (with or without symptoms) * No diffuse brain stem tumors * No type 1 neurofibromatosis PATIENT CHARACTERISTICS: Age * 10 and under Performance status * ECOG 0-2 * Lansky 50-100% Life expectancy * Not specified Hematopoietic * Hemoglobin ≥ 8.0 gm/dL * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT \< 2.5 times ULN Renal * Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR * Creatinine ≤ 0.8 mg/dL (age 5 and under) OR ≤ 1.0 mg/dL (age 6 to10) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 2 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunomodulating agents Chemotherapy * No other concurrent anticancer chemotherapy Endocrine therapy * Prior corticosteroids allowed * No concurrent corticosteroids except for the treatment of increased intracranial pressure Radiotherapy * Not specified Surgery * See Disease Characteristics * Prior surgery allowed Other * No other prior therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short Term Feasibility Success | 24 weeks | Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure. |
| Long Term Feasibility Success | 60 weeks | Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Probability of Progression-free Survival (PFS) | 3 years | Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment. |
| Number of Participants Who Experienced Toxic Death | Up to 6 years after the start of protocol therapy | Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin. |
| Total Number of Patients Experiencing a Response | Up to 18 months of protocol therapy | Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease. |
| Percentage Probability of Event-free Survival (EFS) | Six years | Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment. |
| Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia. | Up to 18 months of protocol therapy | Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) Induction therapy: Patients receive carboplatin IV (175/m2) over 1 hour on days 1, 8, 15, and 22; vincristine IV (1.5 mg/m2) on days 1, 8, 15, 22, 29, and 36; and oral temozolomide (200 mg/m2) on days 43-47. Four weeks after the completion of induction therapy, patients achieving stable or responding disease proceed to maintenance therapy. Maintenance therapy: Patients receive carboplatin (175/m2) and temozolomide (200 mg/m2) as in induction therapy and vincristine IV ((1.5 mg/m2) day 1 of weeks 10,11,12. Treatment repeats every 10 weeks for a total of 6 courses in the absence of disease progression.
carboplatin: Given IV
temozolomide: Given orally
vincristine sulfate: Given IV | 66 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Ineligible | 1 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) |
|---|---|
| Age, Continuous | 4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment Australia | 4 participants |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment United States | 61 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 64 |
| serious Total, serious adverse events | 6 / 64 |
Outcome results
Primary
Long Term Feasibility Success
Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success.
Time frame: 60 weeks
Population: Fourteen (14) patients were considered not evaluable for long-term toxicity because: ineligible - 1 patient; progression during induction - 9 patients; progression during maintenance 2 patients; parent preference - 1 patient and infection resulting in termination of protocol therapy - 1 patient.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Long Term Feasibility Success | 41 participants |
Primary
Short Term Feasibility Success
Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage. Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure.
Time frame: 24 weeks
Population: Fourteen (14) patients were considered not evaluable for short-term toxicity because: ineligible - 1 patient; progression during induction - 9 patients; progression during maintenance 2 patients; parent preference - 1 patient and infection resulting in termination of protocol therapy - 1 patient.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Short Term Feasibility Success | 25 participants |
Secondary
Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.
Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy.
Time frame: Up to 18 months of protocol therapy
Population: Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia. | 43 Participants |
Secondary
Number of Participants Who Experienced Toxic Death
Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin.
Time frame: Up to 6 years after the start of protocol therapy
Population: Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Number of Participants Who Experienced Toxic Death | 0 Participants |
Secondary
Percentage Probability of Event-free Survival (EFS)
Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment.
Time frame: Six years
Population: Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Percentage Probability of Event-free Survival (EFS) | 40.89 percent probability EFS |
Secondary
Percent Probability of Progression-free Survival (PFS)
Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment.
Time frame: 3 years
Population: Sixty-five (65) eligible patients were enrolled and received protocol therapy. These patients are considered for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Percent Probability of Progression-free Survival (PFS) | 60.59 Percent probability PFS |
Secondary
Total Number of Patients Experiencing a Response
Response as complete response, partial response, stable disease, or progressive disease using three-dimensional imaging measurements (preferable) or two-dimensional imaging measurements, as well as the response in the context of multiple lesions or disseminated disease.
Time frame: Up to 18 months of protocol therapy
Population: Sixty-five (65) eligible patients were enrolled and received protocol therapy. Of these patients, 60 had data submission sufficient to determine response.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Total Number of Patients Experiencing a Response | Complete response | 2 Participants |
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Total Number of Patients Experiencing a Response | Partial response | 15 Participants |
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Total Number of Patients Experiencing a Response | Stable disease | 36 Participants |
| Treatment (Carboplatin, Vincristine Sulfate, Temozolomide) | Total Number of Patients Experiencing a Response | Progressive disease | 7 Participants |