Neoplasms

All Conditions

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Liposarcoma

Histiocytoma, Malignant Fibrous

Chondrosarcoma

Fibrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Hemangiosarcoma

Leiomyosarcoma

Sarcoma, Synovial

Neurofibrosarcoma

Sarcoma, Alveolar Soft Part

Solitary Fibrous Tumors

Hemangiopericytoma

Dermatofibrosarcoma

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

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Recurrence

Fibromatosis, Aggressive

Desmoplastic Small Round Cell Tumor

Chordoma

Mesenchymoma

Neoplasms, Adipose Tissue

Neoplasms, Germ Cell and Embryonal

Neoplasms, Vascular Tissue

Neurofibromatoses

Neurofibroma

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Desmoid Tumor

Malignant Mesenchymoma

Neurofibromatosis

Archived DNA tissue samples are analyzed for frequency of genetic mutations, including SNPs, SNVs, and small deletions and/or insertions, by PCR and mass spectometry (Sequenom MassARRAY). Results are then analyzed to determine whether specific mutations correlate with patient or disease features such as tumor stage, histological grade, or outcome.

laboratory biomarker analysis

Steve Skapek, MD

This research trial studies genes in tissue samples from younger and adolescent patients with soft tissue sarcomas. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors find better ways to treat cancer

Study Subtype: Ancillary/Correlative Observational Study Model: Cohort Time Perspective: Retrospective Biospecimen Retention: Samples With DNA Biospecimen Description: Tissue Study Population Description: Existing NRSTS samples from the COG D9902/ARST0332 studies Sampling Method: Non-Probability Sample

OBJECTIVES:

I. To determine the frequency with which actionable mutations are found in archived non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) tumor specimens using mass spectrometry (MS) analysis of tumor-derived deoxyribonucleic acid (DNA).

OUTLINE:

Archived DNA tissue samples are analyzed for frequency of genetic mutations, including single nucleotide polymorphisms (SNPs), single nucleotide variants (SNVs), and small deletions and/or insertions, by polymerase chain reaction (PCR) and mass spectometry (Sequenom MassARRAY). Results are then analyzed to determine whether specific mutations correlate with patient or disease features such as tumor stage, histological grade, or outcome.

Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas

Observational - Potentially Actionable Mutations in Archived Non-Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS)

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)
Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas	NCT01567046	Childhood Alveo... Childhood Angio... Childhood Desmo... Childhood Epith... Childhood Fibro... Childhood Leiom... Childhood Lipos... Childhood Malig... Childhood Neuro... Childhood Synov... Chordoma Desmoid Tumor Metastatic Chil... Nonmetastatic C... Recurrent Child...	laboratory biom...	- 30 Years	Children's Oncology Group
Cyproheptadine in Preventing Weight Loss in Children Receiving Chemotherapy for Cancer	NCT01132547	Cancer	cyproheptadine ... placebo	2 Years - 21 Years	University of South Florida
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)
Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas	NCT01567046	Childhood Alveo... Childhood Angio... Childhood Desmo... Childhood Epith... Childhood Fibro... Childhood Leiom... Childhood Lipos... Childhood Malig... Childhood Neuro... Childhood Synov... Chordoma Desmoid Tumor Metastatic Chil... Nonmetastatic C... Recurrent Child...	laboratory biom...	- 30 Years	Children's Oncology Group

Spots Global Cancer Trial Database for childhood epithelioid sarcoma