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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


Phase 2
N/A
50 Years
Open (Enrolling)
Both
Sarcoma

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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 CenterNew York, New York  10021