Combination Chemotherapy for Ewing's Sarcoma

Recruiting at102 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: University of Leicester

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without radiation therapy and/or surgery in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work when given with or without peripheral stem cell transplantation, radiation therapy, and/or surgery in treating patients with Ewing's sarcoma.

Research Team

Alan W. Craft, MD

Principal Investigator

Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Ian J. Lewis, MD

Principal Investigator

Leeds Cancer Centre at St. James's University Hospital

Odile Oberlin, MD

Principal Investigator

Gustave Roussy, Cancer Campus, Grand Paris

Heribert F. Juergens, MD

Principal Investigator

University Hospital Muenster

Ruth Ladenstein, MD

Principal Investigator

St. Anna Kinderkrebsforschung

Douglas Hawkins, MD

Principal Investigator

Seattle Children's Hospital

Helmut Gadner, MD, FRCPG

Principal Investigator

St. Anna Kinderkrebsforschung

G. Ulrich Exner, MD

Principal Investigator

Balgrist Universitaetsklinik

Eligibility Criteria

This trial is for patients with Ewing's Sarcoma, a type of bone or soft tissue tumor. Eligible participants are under 50 years old, have tumors that can be removed by surgery (less than 200 mL), and may have certain metastases. The trial excludes those who've had a biopsy over 45 days ago or have conditions not specified here.

Inclusion Criteria

My cancer is a type of Ewing's sarcoma or related.

My disease is either operable, was operated on, needs or doesn’t need immediate radiotherapy, has spread to lungs/pleura or beyond, and it’s been less than 45 days since my definitive biopsy.

My kidney function is normal, with a filtration rate of 60 mL/min or more.

Exclusion Criteria

I have never received chemotherapy.

Treatment Details

Interventions

• Autologous Hematopoietic Stem Cell Transplantation (Procedure)
• Busulfan (Alkylating agents)
• Conventional Surgery (Procedure)
• Dactinomycin (Antitumor antibiotic)
• Doxorubicin Hydrochloride (Alkylating agents)
• Etoposide (Topoisomerase II inhibitor)
• Ifosfamide (Alkylating agents)
• Melphalan (Alkylating agents)
• Radiation Therapy (Radiation)
• Vincristine Sulfate (Vinca alkaloids)

Trial Overview The study tests different chemotherapy combinations with options like stem cell transplantation, radiation therapy, and surgery to see which is more effective against Ewing's Sarcoma. Patients will be randomly assigned to receive either just chemo or chemo plus other treatments.

Participant Groups

Group I: Group 2, arm II Experimental Treatment 10 Interventions

Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive high-dose chemotherapy comprising oral busulfan every 6 hours on days -6 to -3 and melphalan IV over 30 minutes on day -2. Patients receive autologous PBSC IV on day 0. Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent radiotherapy 5 days a week for at least 5 weeks.

Group II: Group 2, arm I Experimental Treatment 7 Interventions

Patients undergo 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Some patients may then undergo surgical resection of the tumor. All patients receive VAI chemotherapy as in group 1 for 1 course. Patients then receive 7 additional courses of VAI chemotherapy (courses 8-14). Patients with unresectable, partially resected, or inadequately resected disease undergo concurrent whole-lung radiotherapy for 6-12 days.

Group III: Group 1 Experimental Treatment 7 Interventions

Patients receive 2 additional courses of VIDE induction chemotherapy (courses 5 and 6). Patients requiring radiotherapy to the axial tumor also undergo concurrent radiotherapy 5 days a week. Some patients may then undergo surgical resection of the tumor. All patients will then receive vincristine IV on day 1 and dactinomycin IV and ifosfamide IV over 3 hours on days 1 and 2 (VAI). Treatment repeats every 21 days for 8 courses (courses 7-14). Patients requiring radiotherapy to the brain and/or spinal cord also undergo concurrent radiotherapy.

Busulfan is already approved in Canada, Japan for the following indications:

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

University of Leicester

Lead Sponsor

Trials

218

Recruited

17,750,000+

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Collaborator

Trials

12

Recruited

10,100+

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Austria

Collaborator

Trials

2

Recruited

1,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Societe Francaise Oncologie Pediatrique

Collaborator

Trials

5

Recruited

2,700+

EBMT Solid Tumors Working Party

Collaborator

Trials

5

Recruited

2,300+

Children's Cancer and Leukaemia Group

Collaborator

Trials

56

Recruited

10,700+

German Society for Pediatric Oncology and Hematology GPOH gGmbH

Collaborator

Trials

15

Recruited

14,500+

Swiss Group for Clinical Cancer Research

Collaborator

Trials

138

Recruited

20,300+

Vincent Gruntz

Swiss Group for Clinical Cancer Research

Chief Executive Officer

Economist

Prof. Dr. med. Christoph Rochlitz

Swiss Group for Clinical Cancer Research

Chief Medical Officer since 2022

MD

European Organisation for Research and Treatment of Cancer - EORTC

Collaborator

Trials

417

Recruited

166,000+

Dr. Vassilis Golfinopoulos

European Organisation for Research and Treatment of Cancer - EORTC

Chief Medical Officer

MD

Dr. Denis Lacombe

European Organisation for Research and Treatment of Cancer - EORTC

Chief Executive Officer

MD, MSc