Trial Information

Randomized Study of Vincristine, Actinomycin-D, and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine, Topotecan and Cyclophosphamide for Patients With Intermediate Risk Rhabdomyosarcoma

OBJECTIVES:

I. Compare the early response rates, failure-free survival, and survival of patients with
intermediate-risk rhabdomyosarcoma treated with surgery, radiotherapy, and vincristine,
dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine, topotecan, and
cyclophosphamide.

II. Compare the acute and late effects of these two treatment regimens in these patients.

III. Determine the rate of second-look surgery in selected patients with bulk residual tumor
at diagnosis (i.e., Clinical Group III) and the proportion of these that render the patient
tumor free or with microscopic tumor only.

IV. Determine the rate of local failure in selected patients with bulk residual tumors at
diagnosis (i.e., Clinical Group III) who, after second-look resection, have
response-adjusted radiotherapy dose reduction.

V. Determine if preoperative radiotherapy followed by second-look surgery is feasible for
selected patients with bulk residual disease (i.e., Clinical Group III) who respond poorly
to induction chemotherapy.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
disease (embryonal histology, stage II or III, Clinical Group III vs embryonal histology,
Clinical Group IV, less than 10 years of age vs alveolar or undifferentiated sarcoma
histology, stage I, Clinical Group I vs alveolar or undifferentiated sarcoma histology,
stage II or III, Clinical Group II or III). Patients are randomized to 1 of 2 treatment
arms.

Arm I: Patients receive vincristine IV over 5-10 minutes once a week on weeks 0-12, 15,
18-24, 27, 30-36, and 39. Dactinomycin IV is administered over 15-20 minutes once a week on
weeks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV is administered
over 30-60 minutes once a week on weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and
39. After the initial 12 weeks of chemotherapy, depending on tumor shrinkage, patients may
undergo surgery. After recovery from surgery, patients receive radiotherapy once a day, 5
days a week, during weeks 12-18. For patients receiving radiotherapy during weeks 0-6,
dactinomycin is omitted during weeks 3 and 6 and administered during weeks 15 and 18. For
patients receiving radiotherapy during weeks 12-18, dactinomycin is omitted during weeks 15
and 18. Patients showing an adequate response at week 24 continue chemotherapy during weeks
24-39.

Patients with Clinical Group III tumors of a parameningeal site with documented evidence of
intracranial extension receive radiotherapy within the first 2 weeks of the initiation of
the first course of chemotherapy (day 0).

Patients with Clinical Group II parameningeal tumors and Clinical Group III parameningeal
tumors with base of skull erosion and/or cranial nerve palsy without evidence of
intracranial extension receive radiotherapy on week 12 (day 84) or immediately thereafter.

Patients with Clinical Group IV parameningeal tumors with distant metastases receive
radiotherapy to the primary site on week 12 (day 84). Patients with distant metastases
confined to one site may receive radiotherapy to the metastatic site concurrently with
therapy to the primary site if it began within 2 weeks of the initiation of chemotherapy
(day 0).

Arm II: Patients receive treatment as in arm I, except dactinomycin is replaced with
topotecan IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39.

All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24
hours after completion of each course of chemotherapy and continuing 1 year, until
hematopoietic recovery.

Patients are followed every 1-2 months for 1 year, every 3 months for 1 year, every 6 months
for 1 year, and then annually thereafter.