Ignite Creation Date:
2024-05-05 @ 11:36 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00084838
Status:
COMPLETED
Last Update Posted:
2015-12-24
First Post:
2004-06-10
Brief Title:
Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS ATRT
Sponsor:
Dana-Farber Cancer Institute
Organization:
Dana-Farber Cancer Institute
Study Overview
Official Title:
A Phase II Study of Intrathecal and Systemic Chemotherapy With Radiation Therapy for Children With Central Nervous System Atypical TeratoidRhabdoid Tumor ATRT Tumor
Status:
COMPLETED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die Radiation therapy uses high-energy x-rays to damage tumor cells Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells
PURPOSE This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system CNS atypical teratoidrhabdoid tumors
PURPOSE This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system CNS atypical teratoidrhabdoid tumors
Detailed Description:
OBJECTIVES
Primary
Determine the efficacy of intensive systemic and intrathecal chemotherapy and radiotherapy in terms of medial survival in children with newly diagnosed central nervous system atypical teratoidrhabdoid tumors in comparison with historical outcomes from prior trials
Secondary
Determine the toxicity profile and tolerability of this regimen in these patients
Determine the chemosensitivity of these patients tumors by Magnetic Resonance Imaging MRI after an attempt at maximum surgical resection after 2 courses of this regimen
Determine the predictive value of the INI-1 gene mutation in determining prognosis by comparing tumor samples from patients with vs without this mutation treated with this regimen
STATISTICAL DESIGN This was a single arm design evaluating median overall survival The chosen historical control estimate of 7 months was based on 2 large multi-institutional studies in a similar setting and the alternative of 205 months based on a DFCI pilot study There was 90 power to detect this improvement assuming 1-sided 010 alpha and 17 eligible patients Sample size n20 patients was inflated for expected 10-15 ineligible rate
TREATMENT Induction chemotherapy was required to be initiated within 50 days of the most definitive surgery
Central Nervous System CNSintrathecal therapy All patients with M0 disease receive triple intrathecal IT chemotherapy comprising methotrexate MTX cytarabine and hydrocortisone on day 1 of weeks 1 2 4 7 13 19 27 33 39 45 and 51 followed by oral or intravenous IV leucovorin calcium given 24 hours after each MTX dose Patients with initially positive cerebrospinal fluid CSF cytology M receive triple IT chemotherapy weekly until 2 consecutive CSF samples are negative for malignant cells
Pre-irradiation induction therapy weeks 1-6 Patients receive vincristine IV on day 1 of weeks 1-6 cisplatin IV over 8 hours on day 1 and doxorubicin IV continuously over 48 hours beginning on day 2 of weeks 1 and 4 cyclophosphamide IV continuously over 72 hours beginning on day 2 of week 1 etoposide IV over 1 hour on days 1-3 of week 4 and filgrastim G-CSF subcutaneously SC beginning on day 6 of week 1 and day 4 of week 4 and continuing until blood counts recover
Induction chemoradiotherapy weeks 7-12 Patients receive vincristine IV on day 1 of weeks 7-12 cisplatin IV over 8 hours on day 1 cyclophosphamide IV over 1 hour on day 2 etoposide IV over 1 hour on days 1-3 of weeks 7 and 10 and granulocyte-colony stimulating factor G-CSF subcutaneous SC daily beginning on day 4 of weeks 7 and 10 and continuing until blood counts recover Patients with M0 disease and patients under 3 years of age with M disease undergo radiotherapy to the primary tumor daily on weeks 7-12 Patients 3 years of age and over with M disease undergo craniospinal irradiation CSI daily on weeks 7-12 until negative cerebral spinal fluid CSF cytology is achieved
Post-radiation induction therapy weeks 13-18 Patients receive vincristine IV on day 1 of weeks 13 and 16 doxorubicin and cyclophosphamide as in pre-irradiation induction therapy beginning on day 1 of week 13 cyclophosphamide IV over 1 hour on days 1-3 of week 16 dactinomycin IV on days 1-5 of week 16 and G-CSF SC daily beginning on day 6 of weeks 13 and 16 and continuing until blood counts recover
Maintenance chemotherapy weeks 19-42 Patients receive vincristine IV on day 1 of weeks 27 33 and 39 and days 1 and 5 of weeks 30 36 and 42 doxorubicin and cyclophosphamide as in pre-irradiation induction beginning on day 1 of weeks 27 and 33 doxorubicin IV over 15 minutes and dexrazoxane DX IV over 15 minutes on days 1 and 2 of week 39 cyclophosphamide IV over 1 hour on days 1-3 of weeks 30 36 39 and 42 dactinomycin IV on days 1-5 of weeks 30 36 and 42 and on day 1 of weeks 19 and 23 oral temozolomide on days 1-5 of weeks 19 and 23 and G-CSF SC daily beginning on day 6 of weeks 19 23 30 36 and 42 day 5 of weeks 27 and 33 and day 4 of week 39 and continuing until blood counts recover
Doxorubicin continuation therapy for patients not receiving CSI and mediastinal radiotherapyweeks 45-51 Patients receive vincristine IV on day 1 of weeks 45 48 and 51 and day 5 of week 48 doxorubicin IV over 15 minutes and DX IV over 15 minutes on days 1 and 2 of weeks 45 and 51 cyclophosphamide IV over 1 hour on days 1-3 of weeks 45 48 and 51 dactinomycin IV on days 1-5 of week 48 and G-CSF SC daily beginning on day 4 of weeks 45 and 51 and day 6 of week 48 and continuing until blood counts recover
Non-doxorubicin continuation therapy for patients receiving CSI or mediastinal radiotherapyweeks 45-51 Patients receive cyclophosphamide and G-CSF as in doxorubicin continuation therapy vincristine IV on days 1 and 5 of weeks 45 48 and 51 and dactinomycin IV on days 1-5 of weeks 45 48 and 51
Treatment continues in the absence of disease progression or unacceptable toxicity
Primary
Determine the efficacy of intensive systemic and intrathecal chemotherapy and radiotherapy in terms of medial survival in children with newly diagnosed central nervous system atypical teratoidrhabdoid tumors in comparison with historical outcomes from prior trials
Secondary
Determine the toxicity profile and tolerability of this regimen in these patients
Determine the chemosensitivity of these patients tumors by Magnetic Resonance Imaging MRI after an attempt at maximum surgical resection after 2 courses of this regimen
Determine the predictive value of the INI-1 gene mutation in determining prognosis by comparing tumor samples from patients with vs without this mutation treated with this regimen
STATISTICAL DESIGN This was a single arm design evaluating median overall survival The chosen historical control estimate of 7 months was based on 2 large multi-institutional studies in a similar setting and the alternative of 205 months based on a DFCI pilot study There was 90 power to detect this improvement assuming 1-sided 010 alpha and 17 eligible patients Sample size n20 patients was inflated for expected 10-15 ineligible rate
TREATMENT Induction chemotherapy was required to be initiated within 50 days of the most definitive surgery
Central Nervous System CNSintrathecal therapy All patients with M0 disease receive triple intrathecal IT chemotherapy comprising methotrexate MTX cytarabine and hydrocortisone on day 1 of weeks 1 2 4 7 13 19 27 33 39 45 and 51 followed by oral or intravenous IV leucovorin calcium given 24 hours after each MTX dose Patients with initially positive cerebrospinal fluid CSF cytology M receive triple IT chemotherapy weekly until 2 consecutive CSF samples are negative for malignant cells
Pre-irradiation induction therapy weeks 1-6 Patients receive vincristine IV on day 1 of weeks 1-6 cisplatin IV over 8 hours on day 1 and doxorubicin IV continuously over 48 hours beginning on day 2 of weeks 1 and 4 cyclophosphamide IV continuously over 72 hours beginning on day 2 of week 1 etoposide IV over 1 hour on days 1-3 of week 4 and filgrastim G-CSF subcutaneously SC beginning on day 6 of week 1 and day 4 of week 4 and continuing until blood counts recover
Induction chemoradiotherapy weeks 7-12 Patients receive vincristine IV on day 1 of weeks 7-12 cisplatin IV over 8 hours on day 1 cyclophosphamide IV over 1 hour on day 2 etoposide IV over 1 hour on days 1-3 of weeks 7 and 10 and granulocyte-colony stimulating factor G-CSF subcutaneous SC daily beginning on day 4 of weeks 7 and 10 and continuing until blood counts recover Patients with M0 disease and patients under 3 years of age with M disease undergo radiotherapy to the primary tumor daily on weeks 7-12 Patients 3 years of age and over with M disease undergo craniospinal irradiation CSI daily on weeks 7-12 until negative cerebral spinal fluid CSF cytology is achieved
Post-radiation induction therapy weeks 13-18 Patients receive vincristine IV on day 1 of weeks 13 and 16 doxorubicin and cyclophosphamide as in pre-irradiation induction therapy beginning on day 1 of week 13 cyclophosphamide IV over 1 hour on days 1-3 of week 16 dactinomycin IV on days 1-5 of week 16 and G-CSF SC daily beginning on day 6 of weeks 13 and 16 and continuing until blood counts recover
Maintenance chemotherapy weeks 19-42 Patients receive vincristine IV on day 1 of weeks 27 33 and 39 and days 1 and 5 of weeks 30 36 and 42 doxorubicin and cyclophosphamide as in pre-irradiation induction beginning on day 1 of weeks 27 and 33 doxorubicin IV over 15 minutes and dexrazoxane DX IV over 15 minutes on days 1 and 2 of week 39 cyclophosphamide IV over 1 hour on days 1-3 of weeks 30 36 39 and 42 dactinomycin IV on days 1-5 of weeks 30 36 and 42 and on day 1 of weeks 19 and 23 oral temozolomide on days 1-5 of weeks 19 and 23 and G-CSF SC daily beginning on day 6 of weeks 19 23 30 36 and 42 day 5 of weeks 27 and 33 and day 4 of week 39 and continuing until blood counts recover
Doxorubicin continuation therapy for patients not receiving CSI and mediastinal radiotherapyweeks 45-51 Patients receive vincristine IV on day 1 of weeks 45 48 and 51 and day 5 of week 48 doxorubicin IV over 15 minutes and DX IV over 15 minutes on days 1 and 2 of weeks 45 and 51 cyclophosphamide IV over 1 hour on days 1-3 of weeks 45 48 and 51 dactinomycin IV on days 1-5 of week 48 and G-CSF SC daily beginning on day 4 of weeks 45 and 51 and day 6 of week 48 and continuing until blood counts recover
Non-doxorubicin continuation therapy for patients receiving CSI or mediastinal radiotherapyweeks 45-51 Patients receive cyclophosphamide and G-CSF as in doxorubicin continuation therapy vincristine IV on days 1 and 5 of weeks 45 48 and 51 and dactinomycin IV on days 1-5 of weeks 45 48 and 51
Treatment continues in the absence of disease progression or unacceptable toxicity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P30CA006516 | NIH | None | httpsreporternihgovquickSearchP30CA006516 |