Trial Information

Localized Non-Rhabdomyosarcoma Soft Tissue Sarcomas

OBJECTIVES:

Primary

- Determine survival rates (event-free survival and overall survival [OS]) and the
pattern of treatment failure in patients with synovial sarcoma or adult-type soft
tissue sarcoma treated with ifosfamide and doxorubicin hydrochloride, radiotherapy,
and/or surgery.

- Determine the role of ifosfamide and doxorubicin hydrochloride in improving the
response rate in patients with unresectable synovial sarcoma or adult-type soft tissue
sarcoma.

Secondary

- Evaluate clinical/pathological prognostic factors, particularly tumor grade and
radiological and pathological response to neoadjuvant treatment.

- Determine the impact of omitting adjuvant chemotherapy in patients with low-risk
synovial sarcoma (tumor < 5 cm).

- Determine the role of adjuvant chemotherapy in improving the metastases-free survival
and OS in patients with adult-type soft tissue sarcoma (Intergroup Rhabdomyosarcoma
Study [IRS] postsurgical grouping system I-II, tumor grade 3, tumor size > 5 cm).

OUTLINE: This is a nonrandomized, prospective, historically controlled, multicenter study.
Patients with synovial sarcoma are stratified according to the Intergroup Rhabdomyosarcoma
Study (IRS) postsurgical grouping system (I vs II vs III) and tumor size ( ≤ 5 cm vs > 5
cm). Patients with adult-type soft tissue sarcoma are stratified according to the IRS
postsurgical grouping system (I vs II vs III), tumor size ( ≤ 5 cm vs > 5 cm), and tumor
grade (G1 vs G2 vs G3). Patients are assigned to 1 of 9 treatment groups according to
disease and stratification.

Synovial sarcoma

- Group 1 (IRS group I, tumor ≤ 5 cm): Patients undergo surgical resection of tumor.

- Group 2 (IRS group I, tumor > 5 cm): Patients receive ifosfamide IV over 3 hours on
days 1-3 and doxorubicin hydrochloride IV over 4-6 hours on days 1 and 2 (IFO-DOX).
Treatment repeats every 21 days for 4 courses.

- Group 3 (IRS group II, tumor ≤ 5 cm): Patients receive 3 courses of IFO-DOX. After the
completion of chemotherapy, patients undergo radiotherapy 5 days a week for 5-6 weeks.

- Group 4 (IRS group II, tumor > 5 cm): Patients receive 3 courses of IFO-DOX. Patients
then receive ifosfamide alone IV over 3 hours on days 1-3. Treatment with ifosfamide
repeats every 21 days for 2 courses. Patients also receive concurrent radiotherapy
(concurrently with ifosfamide) 5 days a week for 5-6 weeks. After completion of
radiotherapy, patients receive 1 additional course of IFO-DOX.

- Group 5 (IRS group III, N1): Patients receive 3 courses of IFO-DOX. Patients with no
response to chemotherapy receive 1 of the following local therapies:

- Delayed complete resection*

- Radiotherapy (as in group 3) followed by surgery*

- Delayed complete resection* followed by radiotherapy** (as in group 3)

- Delayed incomplete resection* followed by radiotherapy** (as in group 3)

- Radiotherapy (as in group 3) Patients with major or minor response to chemotherapy
receive 2 courses of ifosfamide with concurrent radiotherapy followed by 1
additional course of IFO-DOX (as in group 4, above).

NOTE: * Patients undergo surgery 5 weeks after completion of chemotherapy and/or
radiotherapy.

NOTE: **Patients undergo radiotherapy beginning < 21 days after surgery.

Adult-type soft tissue sarcoma

- Group 1 (IRS group I, tumor ≤ 5 cm): Patients undergo surgical resection of tumor.

- Group 2 (IRS group I, tumor > 5 cm): Patients receive therapy according to tumor grade:

- G1 disease: Patients undergo surgical resection.

- G2 disease: Patients undergo radiotherapy 5 days a week for 5-6 weeks.

- G3 disease: Patients receive the following sequential treatment: 3 courses of
IFO-DOX followed by 2 courses of ifosfamide with concurrent radiotherapy followed
by 1 course of IFO-DOX.

- Group 3 (IRS group II, N0): Patients receive therapy according to tumor grade:

- G1 disease: Patients undergo surgical resection.

- G2-3 disease (≤ 5 cm) and G2 disease (> 5 cm): Patients undergo radiotherapy 5
days a week for 5-6 weeks.

- G3 disease (> 5 cm): Patients undergo sequential treatment (as in group 2,
adult-type soft tissue sarcoma).

- Group 4 (IRS group III, N1): Patients receive 3 courses of IFO-DOX. Patients with no
response to chemotherapy receive local therapy (as in group 5 synovial sarcoma).
Patients with major or minor response to chemotherapy receive 2 courses of ifosfamide
with concurrent radiotherapy followed by 2 additional courses of IFO-DOX (as in group
4, synovial sarcoma).

After completion of study therapy, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 250 patients will be accrued for this study.