Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

NCT01946529 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: ESFT13NCI-2013-01657
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol will study treatment for Ewing sarcoma family of tumors (ESFT) and desmoplastic small round cell tumor (DSRCT). Participants with ESFT will be divided into two treatment groups, A or B, based on tumor characteristics. Group A (standard risk) participants have tumor that is not in the pelvis, has not spread to other parts of the body, and are less than 14 years of age. Because previous clinical trials have shown that standard treatment is very effective for children whose tumors have these characteristics, these participants will receive standard treatment. Group B (high risk) participants are 14 years of age or older or have tumor in the pelvis, or the tumor has spread to other parts of the body. Participants with DSRCT in the abdomen and/or pelvis or with tumor that cannot be removed by surgery alone or has spread to other parts of the body will be included in Group B. Participants in this group are considered high risk because there is a greater chance of tumor recurring following standard treatments currently in use. All participants will be followed and evaluated for 10 years following completion of therapy.

Conditions

Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Outcome Measures

Primary Outcomes (1)

• Response to Window Therapy (2 Courses) for Group B (High-risk) - ESFT Participants

  Response rate will be defined as the proportion of patients who achieved complete response or partial response (CR+PR) using the World Health Organization (WHO) criteria evaluated after two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high risk Ewing Sarcoma Family of Tumor (ESFT). Participants who are treated in Group B with Desmoplastic Small Round Cell Tumor (DSRCT) or those who do not receive window therapy will not be included in this analysis.

  at 6 weeks after start of therapy (after 2 initial courses)

Secondary Outcomes (4)

• Overall Survival

  Maximum of 11 years after the start of therapy

• Progression-free Survival

  Maximum of 11 years after the start of therapy

• Time to Progression

  Maximum of 11 years after the start of therapy

• Local Failure Rate

  Maximum of 11 years after the start of therapy

Study Arms (2)

Group A (Standard Risk)

ACTIVE COMPARATOR

Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m\^2. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.

Drug: vincristine; Drug: doxorubicin; Drug: cyclophosphamide; Drug: ifosfamide; Drug: etoposide; Procedure: surgery; Radiation: radiation

Group B (High Risk)

ACTIVE COMPARATOR

Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, irinotecan, temozolomide, temsirolimus, bevacizumab, and sorafenib. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone or surgery followed by radiation.

Drug: doxorubicin; Drug: cyclophosphamide; Drug: ifosfamide; Drug: etoposide; Drug: temozolomide; Drug: temsirolimus; Drug: bevacizumab; Drug: sorafenib; Procedure: surgery; Radiation: radiation

Interventions

vincristine DRUG

Dosage and route of administration: Infants \< 12 months of age: 0.05 mg/kg IV day 1; participants ≥ 12 months of age: 1.5 mg/m\^2 IV day 1 (max. dose 2 mg).

Also known as: Oncovin(R)

Group A (Standard Risk)

doxorubicin DRUG

Dosage and route of administration: Infants \< 1 year 2.5 mg/kg continuous infusion (CI) over 48 hours, days 1-2; participants \> 1 year of age 75 mg/m\^2 CI over 48 hours, days 1-2.

Also known as: Adriamycin(R)

Group A (Standard Risk); Group B (High Risk)

cyclophosphamide DRUG

Dosage and route of administration: The dose and route are different in neo-adjuvant/adjuvant chemotherapy and maintenance therapy. Please see the Detailed Description for further information.

Also known as: Cytoxan(R)

Group A (Standard Risk); Group B (High Risk)

ifosfamide DRUG

Dosage and route of administration: Infants \< 1 year of age 60 mg/kg/day IV over 60 minutes days 1-5; participants \> 12 months of age 1800 mg/m\^2 IV over 60 minutes x 5 days, days 1-5.

Also known as: Ifex(R)

Group A (Standard Risk); Group B (High Risk)

etoposide DRUG

Dosage and route of administration: Infants \< 1 year of age 3.3 mg/kg/day IV over 60 minutes days 1-5; children \> 1 year 100 mg/m\^2 daily IV over 60 minutes days 1-5.

Also known as: VP-16, Vepesid(R)

Group A (Standard Risk); Group B (High Risk)

temozolomide DRUG

Dosage and route of administration: Temozolomide 100 mg/m\^2 PO once daily, days 1-5.

Also known as: Temodar(R)

Group B (High Risk)

temsirolimus DRUG

Dosage and route of administration: Temsirolimus 35 mg/m\^2 IV once day 1 and day 8.

Also known as: CCI-779, Torisel^TM

Group B (High Risk)

bevacizumab DRUG

Dosage and route of administration: Bevacizumab 15 mg/kg IV on day 1 every 3 weeks.

Also known as: rhumab VEGF, Avastin(R)

Group B (High Risk)

sorafenib DRUG

Dosage and route of administration: 90 mg/m\^2/dose PO BID

Also known as: BAY-43-9006, Nexavar(R)

Group B (High Risk)

surgery PROCEDURE

If participant meets the criteria, they will have surgical resection of their tumor.

Also known as: therapeutic conventional surgery

Group A (Standard Risk); Group B (High Risk)

radiation RADIATION

If the participant meets the criteria, participants will receive radiation therapy. Chemotherapy will continue during radiation.

Also known as: proton beam radiation therapy, external beam radiation therapy, brachytherapy

Group A (Standard Risk); Group B (High Risk)

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Group A participants must be \<14 years of age at time of diagnosis of histologically proven non-pelvic localized Ewing sarcoma family of tumor (ESFT) involving the bone or soft tissue.
• Group B participants must have newly diagnosed of histologically proven ESFT involving the bone or soft tissue and at least one of the following: metastatic disease (must be biopsy proven), or pelvic primary, or ≥14 years of age at the time of diagnosis.
• OR Group B participants must be newly diagnosed with intra-abdominal, unresectable or metastatic desmoplastic small round cell tumor. Metastatic site must be biopsy proven.
• Age must be ≤25 years.
• Adequate bone marrow function defined as a peripheral absolute neutrophil count (ANC) ≥750/m\^3 and platelet count ≥75,000/m\^3 (no transfusion within 7 days of study enrollment). Patients with Ewing sarcoma metastatic to the bone marrow are not required to meet bone marrow criteria for study eligibility and are not evaluable for hematologic toxicity.
• Must have adequate renal function based on age.
• Must not have had prior chemotherapy or radiation therapy. Emergent radiotherapy to preserve vital organ function is permitted. Participants who receive emergent radiation will not be eligible for window therapy.
• Must have adequate hepatic function defined as total bilirubin ≤3.0 mg/dL.
• Must have adequate cardiac function defined as shortening fraction ≥28%.
• Females of childbearing potential and males able to father a child must be willing to practice acceptable methods of birth control to prevent pregnancy.
• Additional criteria for Group B participants who will receive upfront window therapy (does not apply to participants who opt out of window therapy):
• Cytochrome P450 CYP3A4 active agents: Must not be taking any of the following potent CYP3A4 inducers or inhibitors within 1 week prior to study entry: azole antifungals (such as fluconazole, voriconazole, itraconazole, ketoconazole), rifampin, phenytoin, phenobarbitol, carbamazepine, grapefruit juice and St. John's wort.
• Must have measurable disease.
• Must not have received emergent radiation therapy.
• Serum triglyceride level ≤ 300 mg/dL and serum cholesterol ≤ 300 mg/dL.

You may not qualify if:

• Participant is pregnant or breastfeeding.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
• Participant has a prior history of malignancy, with the exception of non-melanoma skin cancer. Participants with history of skin cancer must have 5 years elapse since that diagnosis, be in remission, and must not have received chemotherapy, immunotherapy, or radiation therapy.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• University of Tennessee: collaborator
• University of Florida: collaborator
• Nemours Children's Clinic: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Desmoplastic Small Round Cell Tumor; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Vincristine; Doxorubicin; Cyclophosphamide; Ifosfamide; Etoposide; Temozolomide; temsirolimus; Bevacizumab; Sorafenib; Surgical Procedures, Operative; Radiation; Proton Therapy; Brachytherapy

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Dacarbazine; Triazenes; Imidazoles; Azoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Physical Phenomena; Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Limitations and Caveats

Interim analysis to evaluate efficacy of the therapy determined that the window therapy did not meet the anticipated response, and trial accrual was stopped. Some patients continue on therapy.

Results Point of Contact

• Title: Sara Federico, MD
• Organization: St. Jude Children's Research Hospital

sara.federico@stjude.org

901-595-2220

Study Officials

• Sara M. Federico, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 19, 2013
• Study Start: December 27, 2013
• Primary Completion: August 1, 2015
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 23, 2026
• Results First Posted: October 19, 2016

Record last verified: 2026-02

Locations

US (1)