Neoplasms

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Rare Diseases

Sarcoma

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Hemangiopericytoma

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Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Epithelioid Sarcoma

Alveolar Soft Part Sarcoma

Dermatofibrosarcoma Protuberans

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Ifosfamide

Isophosphamide mustard

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

doxorubicin hydrochloride

ifosfamide

adjuvant therapy

conventional surgery

neoadjuvant therapy

radiation therapy

Ruth Ladenstein, MD

Nadine Francotte, MD

Catherine Rechnitzer, MD, PhD

Daniel Orbach, MD

Anne O'Meara, MD

Soledad Gallego, MD, PhD

Gustaf Ljungman, MD

Felix Niggli, MD

David Hobin, MD

M. C. G. Stevens, MD

Denise Williams, MD

Adam Glaser, MD

Johann Visser, MD

Heather P. McDowell, MD

Ananth Shankar, MD

Julia Chisholm, MD

Bernadette Brennan, MD

Juliet Hale, MD

Martin Hewitt, MD, BSc, FRCP, FRCPCH

Kate Wheeler, MD

Mary P. Gerrard, MBChB, FRCP, FRCPCH

Janice A. Kohler, MD, FRCP

Kathy Pritchard-Jones, MD

Anthony McCarthy, MD

Derek King, MD

W. Hamish Wallace, MD

Milind D. Ronghe, MD

Heidi Traunecker, MD, PhD

Andrea Ferrari, MD

Modesto Carli, MD

Joern Treuner, MD

Max Van Noesel, MD, PhD

RATIONALE: Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy with or without radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase III trial is studying how well giving ifosfamide and doxorubicin, radiation therapy, and/or surgery works in treating young patients with localized soft tissue sarcoma.

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.

Ifosfamide and Doxorubicin, Radiation Therapy, and/or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma

Localized Non-Rhabdomyosarcoma Soft Tissue Sarcomas

Italian Association for Pediatric Hematology Oncology

Cooperative Weichteilsarkom Studie

Children's Cancer and Leukaemia Group

Dutch Childhood Oncology Group

European Paediatric Soft Tissue Sarcoma Study Group

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Celecoxib

Cyclooxygenase 2 Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

celecoxib

Aaron H. Wolfson, MD

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving celecoxib together with radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with radiation therapy in treating patients with stage II or stage III soft tissue sarcoma of the arm, hand, leg, or foot that has been removed by surgery.

OBJECTIVES:

* Determine the maximum tolerated dose of adjuvant celecoxib administered with radiotherapy in patients with resected stage II or III soft tissue sarcoma of the extremity.

OUTLINE: This is a dose-escalation study of celecoxib.

Beginning within 10 weeks of the most recent resection, patients undergo standard radiotherapy once daily, 5 days a week, in weeks 1-7. Patients also receive oral celecoxib twice daily in weeks 1-7 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of celecoxib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. A maximum of 6 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Celecoxib and Radiation Therapy in Treating Patients With Stage II or Stage III Soft Tissue Sarcoma of the Arm, Hand, Leg, or Foot That Has Been Removed by Surgery

A Phase I Trial of Postoperative Radiation With Dose-Escalation of A Cox-2 Inhibitor, Celebrex™ (CELECOXIB) in Patients With Soft Tissue Sarcoma of the Extremity

University of Miami

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ifosfamide and Doxorubicin, Radiation Therapy, and/or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma	NCT00334854	Childhood Malig... Sarcoma	doxorubicin hyd... ifosfamide adjuvant therap... conventional su... neoadjuvant the... radiation thera...	- 20 Years	National Cancer Institute (NCI)
Celecoxib and Radiation Therapy in Treating Patients With Stage II or Stage III Soft Tissue Sarcoma of the Arm, Hand, Leg, or Foot That Has Been Removed by Surgery	NCT00450736	Childhood Malig... Sarcoma	celecoxib adjuvant therap... radiation thera...	18 Years - 120 Years	University of Miami
Ifosfamide and Doxorubicin, Radiation Therapy, and/or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma	NCT00334854	Childhood Malig... Sarcoma	doxorubicin hyd... ifosfamide adjuvant therap... conventional su... neoadjuvant the... radiation thera...	- 20 Years	National Cancer Institute (NCI)
Celecoxib and Radiation Therapy in Treating Patients With Stage II or Stage III Soft Tissue Sarcoma of the Arm, Hand, Leg, or Foot That Has Been Removed by Surgery	NCT00450736	Childhood Malig... Sarcoma	celecoxib adjuvant therap... radiation thera...	18 Years - 120 Years	University of Miami

Spots Global Cancer Trial Database for childhood malignant hemangiopericytoma