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
N/A
50 Years
Both
Sarcoma
Trial Information
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.
Inclusion Criteria
INCLUSION CRITERIA:
- Newly diagnosed, previously untreated histologically-proven rhabdomyosarcoma,
undifferentiated sarcoma, or ectomesenchymoma. Histology must be confirmed by a MSKCC
pathologist.
Intermediate- or high-risk features as defined below:
- All patients with Stage 4 tumors (distant metastases).
Intermediate Risk:
- All patients with non-metastatic undifferentiated sarcoma or alveolar RMS or
ectomesenchymoma with alveolar features (regardless of age, site, size, stage, or
degree of initial surgical resection);
- All patients < 1 year of age with non-metastatic embryonal RMS or ectomesenchymoma
with embryonal features (regardless of site, stage, or degree of initial surgical
resection).
- Patients ≥ 1 year of age with Stage 2 or 3 (unfavorable site [see Appendix I] and
either size > 5 cm, OR regional nodes positive, or both), Group III (gross residual
disease post-biopsy or attempted resection) embryonal RMS or ectomesenchymoma with
embryonal features
- Age: ≤ 50 years (inclusive) at the time of diagnosis.
- Biopsy or definitive surgery within 42 days of start of treatment.
Organ function:
- Normal renal function: Normal serum creatinine for age or creatinine clearance or
nuclear GFR of ≥ 80 ml/min/1.73m2 (in the absence of obstructive hydronephrosis,
e.g., from pelvic or bladder/prostate tumor).
- Normal liver function: Total bilirubin, SGOT/SGPT < 2.5 times the upper limit of
normal (in the absence of hepatic involvement by tumor)
- Normal cardiac function: echocardiogram shortening fraction ≥ 28% or resting left
ventricular ejection fraction (LVEF) ≥ 50% on Technetium-99m pertechnetate
radionuclide cineangiography (MUGA)
- Normal hematologic function: absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥
9 gm/dL, and platelet count ≥ 100,000/μL (in the absence of bone marrow infiltration
by tumor or the presence of disseminated intravascular coagulation).
- Measurable disease is not required.
- Patients must consent to an indwelling central venous catheter.
- Sexually active patients of childbearing potential must be willing to use an
effective method of contraception.
- Patient or guardian must be capable of providing informed consent.
SUBJECT EXCLUSION CRITERIA:
- Prior chemotherapy or radiotherapy (other than limited, emergent radiotherapy for
treatment of threatened airway or cord compromise).
- Pregnant or breast feeding females because the chemotherapy administered on this
trial could have a detrimental effect on the developing fetus or newborn.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Leonard H. Wexler, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
03-099
NCT ID:
NCT00077285
Start Date:
October 2003
Completion Date:
October 2013
Related Keywords:
- Sarcoma
- previously untreated childhood rhabdomyosarcoma
- embryonal childhood rhabdomyosarcoma
- alveolar childhood rhabdomyosarcoma
- adult rhabdomyosarcoma
- stage IV adult soft tissue sarcoma
- metastatic childhood soft tissue sarcoma
- nonmetastatic childhood soft tissue sarcoma
- childhood malignant mesenchymoma
- adult malignant mesenchymoma
- stage III adult soft tissue sarcoma
- stage II adult soft tissue sarcoma
- stage I adult soft tissue sarcoma
- Rhabdomyosarcoma
- Sarcoma
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
