A Pilot Phase II Trial Of Irinotecan Plus Carboplatin, And Irinotecan Maintenance Therapy (High-Risk Patients Only), Integrated Into The Upfront Therapy Of Newly Diagnosed Patients With Intermediate - And High-Risk Rhabdomyosarcoma
OBJECTIVES:
Primary
- Determine the response rate in patients with newly diagnosed intermediate- or high-risk
rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and
carboplatin.
- Determine the acute toxic effects of this regimen combined with radiotherapy in these
patients.
- Determine the safety and feasibility of this regimen in these patients.
- Determine the rate of local control achieved in patients treated with this regimen in
combination with intensity-modulated radiotherapy.
- Determine the safety and feasibility of administering maintenance therapy comprising
irinotecan to patients with high-risk rhabdomyosarcoma treated with this regimen.
Secondary
- Correlate, preliminarily, in vitro measurements of angiogenesis with clinical features
(extent of disease), response to therapy, and outcome in patients treated with this
regimen.
- Determine, preliminarily, the efficacy of this regimen, in terms of improved outcomes,
in these patients.
OUTLINE: This is a pilot study.
- Courses 1 and 2: Patients receive carboplatin IV over 1 hour on day 1 and irinotecan IV
over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2
courses.
- Courses 3-5: Patients receive vincristine IV on days 1, 8, and 15; dexrazoxane IV over
15-30 minutes, doxorubicin IV over 15-30 minutes, and cyclophosphamide IV over 1 hour
on days 1 and 2; and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on
approximately day 3 and continuing until blood counts recover. Treatment repeats every
21 days for a total of 3 courses.
Some patients may undergo surgical resection of the tumor after completion of course 5.
After course 5, patients undergo radiotherapy once daily, 5 days a week, for 4-5.5 weeks.
- Courses 6 and 7*: Patients receive vincristine IV and carboplatin IV over 1 hour on day
1; irinotecan IV over 1 hour on days 1-5 and 8-12; and G-CSF SC once daily beginning on
approximately day 13 and continuing until blood counts recover. Treatment repeats every
21 days for a total of 2 courses.
NOTE: *Patients who develop disease progression during courses 1 or 2 do not receive further
irinotecan and carboplatin. Instead, patients receive ifosfamide and etoposide as in courses
8 and 9.
- Courses 8 and 9: Patients receive vincristine IV on day 1; etoposide IV over 1 hour and
ifosfamide IV over 2 hours on days 1-5; and G-CSF SC once daily beginning on
approximately day 6 and continuing until blood counts recover. Treatment repeats every
21 days for a total of 2 courses.
- Course 10: Patients receive vincristine IV on days 1, 8, 15, 22, 29, 36, and 43;
dexrazoxane IV over 15-30 minutes, doxorubicin IV over 15-30 minutes, and
cyclophosphamide IV over 1 hour on days 1 and 2; and filgrastim SC beginning on
approximately day 3 and continuing until blood counts recover (1 course).
- Course 11 and 12: Patients receive etoposide IV over 1 hour and ifosfamide IV over 2
hours on days 1-5 and G-CSF SC once daily beginning on approximately day 6 and
continuing until blood counts recover. Treatment repeats every 21 days for a total of 2
courses.
Patients with high-risk disease proceed to maintenance therapy.
- Maintenance therapy*: Patients receive irinotecan IV over 1 hour on days 1-5 and 8-12.
Treatment repeats every 21 days for a total of 6 courses.
NOTE: *Patients who develop disease progression during courses 1 or 2 do not receive further
irinotecan.
In all courses, treatment continues in the absence of unacceptable toxicity or disease
progression or recurrence after initial response.
Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1
year, and then annually thereafter.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate
2 years
No
Leonard H. Wexler, MD
Principal Investigator
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
03-099
NCT00077285
October 2003
October 2013
Name | Location |
---|---|
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |