ARST0531- Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) versus VAC Alternating with Vincristine and Irinotecan (VI) for Patients with Intermediate-Risk Rhabdomyosarcoma (RMS)

Summary

The following screening tests will be done prior to starting this study.

* Medical history and physical examination

* Urine analysis

* Blood test to evaluate liver, kidney and metabolic function (the chemical and physical changes occurring in the body)

* Blood count (numbers of red and white cells and platelets)

* Scans of the tumor by computed tomography (CT) scan, magnetic resonance imaging (MRI), fluoro-deoxy-glucose positron emission tomography (PET scan) and/or bone scan to measure your tumor size and determine if it has spread

* Bone marrow aspiration and biopsy to see if there are any cancer cells present

* Spinal tap (for patients with cancers near the brain)

* Lymph node biopsy (for patients with cancer in the arms or legs or the testicle of boys older than 10 years)

* Pregnancy test, if applicable

* Demographic information (age, sex, ethnic origin)

Participants will receive one of two different treatment plans. Some participants will be randomized to get Regimen A (which is VAC alone) and some will be randomized to get Regimen B (which is VAC plus VI). For Regimen A, therapy will be given on the same schedule as standard treatment with VAC, but with a slightly lower dose of the standard drug cyclophosphamide. For Regimen B, the experimental drug combination of irinotecan and vincristine is added.

Please see Treatment Diagram, page 2 of project summary.

Procedures and Evaluations during the Research
We hope that some subjects on this study will have PET scans so we can find out if PET scans are good for the diagnosis of sarcomas and good at showing how the tumors respond to therapy. PET scans will be done prior to study entry, at week 4 and week 15 of the study.

Subjects on Regimen A and B may agree to take part in optional testing for cyclophosphamide and irinotecan sensitivity; there are some genetic features that affect how the body uses cyclophosphamide and irinotecan. For these tests, about two teaspoonfuls of blood will be drawn. The results of these research tests will not be given to the subject or his/her study doctor and will not become part of the subject[Right Quote]s health record. The subject will not be charged for these tests. There will be no change in the doses of cyclophosphamide or irinotecan on this study based on the results of the testing. If the subject would like to know the results of the irinotecan sensitivity testing, then they will need to have the test done in a commercial laboratory. This test is optional and will not change the subject[Right Quote]s treatment; therefore, the subject[Right Quote]s insurance company will have to pay to have the UGT1A1 test done at a commercial laboratory.

Standard tests and procedures
The following tests and procedures are part of regular cancer care and may be done even if the subject does not join the study.

* Frequent labs to monitor blood counts and blood chemistries

* Urine tests to measure how the kidneys are functioning

* Pregnancy test for females of childbearing age before treatment begins

* X-rays and scans to monitor the patient[Right Quote]s response to treatment.

* Bone Marrow Aspiration and Biopsy to see if there are any cancer cells present

* Spinal taps (for cancers near the brain)

* Lymph node biopsy (for cancer in the arms or legs or the testicle of boys and amp;gt; 10 years of age)

Participant Eligibility

Age < 50 years at the time of enrollment. Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study. Enrollment on D9902 (IRB File# 0999-398, A COG Soft Tissue Sarcoma Biology and Banking Protocol) to confirm local histologic diagnosis with central pathology review is required for all patients. Patient must have Intermediate-risk RMS defined as: a) Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: Stage 2 or 3 and Group III or b) Alveolar RMS: Stage 1-3 and Group I-III. Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all patients ≥ 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement, defined as two or more lymph nodes > 2 cm in dimension, is identified by imaging studies). Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors. Detection of metastasis by optional FDG PET (not required for study enrollment). Patients must have a performance status of 0, 1, or 2. Strong inhibitors or stimulators of cyctochrome P450 3A4, including azole antifungals (such as fluconazole, voriconazole, itraconazole, ketoconazole) rifamipin, phenytoin, phenobarbitol, carbamazepine, and St. John’s wort, should all be avoided or used with great caution. Aprepitant is known to interact with CYP3A4 and is not permitted during cyclophosphamide chemotherapy. Adequate renal, liver and bone marrow function. No evidence of uncontrolled infection. Patients must be able to undergo Radiation Therapy, if necessary, as specified in the protocol. Female patients of childbearing potential must have a negative pregnancy test. Female patients who are breast feeding must agree to stop breast feeding. Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed. All patients and/or their parents or legal guardians must sign a written informed consent. All institutional, FDA, and NCI requirements for human studies must be met. Spanish speaking subjects are eligible using the Spanish short form consent.