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NCT01231906

Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma

Completed Phase 3 Results posted Last updated 23 January 2026
What this trial tests

Phase 3 trial testing Cyclophosphamide in Localized Extraskeletal Ewing Sarcoma in 642 participants. Completed in 31 December 2025.

Timeline
24 November 2010
Primary endpoint
31 March 2020
31 December 2025

Quick facts

Lead sponsorChildren's Oncology Group
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment642
Start date24 November 2010
Primary completion31 March 2020
Estimated completion31 December 2025
Sites243 locations across New Zealand, Saudi Arabia, Canada, Puerto Rico, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Children's Oncology Group — full company profile →

Who can join

Under 50, any sex, with Localized Extraskeletal Ewing Sarcoma or Peripheral Primitive Neuroectodermal Tumor of Bone. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Event-Free Survival Primary · 5 years after enrollment

Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.

GroupValue95% CI
Arm A (Combination Chemotherapy)77.6472.42 – 81.99
Arm B (Combination Chemotherapy, Topotecan Hydrochloride)78.7973.70 – 83.01

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 6 months post-treatment planned as 252 days; All-Cause Mortality: up to 9 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A (Combination Chemotherapy)
Serious: 8/308 (3%)
Deaths: 51/308
Arm B (Combination Chemotherapy, Topotecan Hydrochloride)
Serious: 11/318 (3%)
Deaths: 42/318

Serious adverse events (39 terms)

ReactionSystemArm A (Combination Chemoth…Arm B (Combination Chemoth…
SepsisInfections and infestations——
AscitesGastrointestinal disorders——
Respiratory failureRespiratory, thoracic and mediastinal disorders——
HypotensionVascular disorders——
AnemiaBlood and lymphatic system disorders——
Febrile neutropeniaBlood and lymphatic system disorders——
Heart failureCardiac disorders——
Left ventricular systolic dysfunctionCardiac disorders——
Right ventricular dysfunctionCardiac disorders——
Sinus tachycardiaCardiac disorders——
ColitisGastrointestinal disorders——
DiarrheaGastrointestinal disorders——
Mucositis oralGastrointestinal disorders——
NauseaGastrointestinal disorders——
Stomach painGastrointestinal disorders——
TyphlitisGastrointestinal disorders——
Hepatic failureHepatobiliary disorders——
Portal hypertensionHepatobiliary disorders——
Allergic reactionImmune system disorders——
Enterocolitis infectiousInfections and infestations——
Infections and infestations - Other, specifyInfections and infestations——
Soft tissue infectionInfections and infestations——
Urinary tract infectionInfections and infestations——
Injury, poisoning and procedural complications - Other, specifyInjury, poisoning and procedural complications——
Alanine aminotransferase increasedInvestigations——
Other adverse events (101 terms — click to expand)

ReactionSystemArm A (Combination Chemoth…Arm B (Combination Chemoth…
Febrile neutropeniaBlood and lymphatic system disorders——
Neutrophil count decreasedInvestigations——
Platelet count decreasedInvestigations——
White blood cell decreasedInvestigations——
AnemiaBlood and lymphatic system disorders——
Infections and infestations - Other, specifyInfections and infestations——
Mucositis oralGastrointestinal disorders——
Pain in extremityMusculoskeletal and connective tissue disorders——
HypokalemiaMetabolism and nutrition disorders——
Joint range of motion decreasedMusculoskeletal and connective tissue disorders——
Back painMusculoskeletal and connective tissue disorders——
PainGeneral disorders——
Lymphocyte count decreasedInvestigations——
Bone painMusculoskeletal and connective tissue disorders——
Chest wall painMusculoskeletal and connective tissue disorders——
HypotensionVascular disorders——
DiarrheaGastrointestinal disorders——
SepsisInfections and infestations——
Wound infectionInfections and infestations——
DehydrationMetabolism and nutrition disorders——
Abdominal painGastrointestinal disorders——
VomitingGastrointestinal disorders——
FeverGeneral disorders——
Alanine aminotransferase increasedInvestigations——
AnorexiaMetabolism and nutrition disorders——
HyperglycemiaMetabolism and nutrition disorders——
HypophosphatemiaMetabolism and nutrition disorders——
ArthralgiaMusculoskeletal and connective tissue disorders——
Generalized muscle weaknessMusculoskeletal and connective tissue disorders——
Muscle weakness lower limbMusculoskeletal and connective tissue disorders——
Musculoskeletal and connective tissue disorder - Other, specifyMusculoskeletal and connective tissue disorders——
Soft tissue necrosis lower limbMusculoskeletal and connective tissue disorders——
Peripheral motor neuropathyNervous system disorders——
Peripheral sensory neuropathyNervous system disorders——
Left ventricular systolic dysfunctionCardiac disorders——
ColitisGastrointestinal disorders——
Gait disturbanceGeneral disorders——
Catheter related infectionInfections and infestations——
Skin infectionInfections and infestations——
Soft tissue infectionInfections and infestations——

Most-reported serious reactions: Sepsis, Ascites, Respiratory failure, Hypotension, Anemia, Febrile neutropenia, Heart failure, Left ventricular systolic dysfunction.

Data from ClinicalTrials.gov NCT01231906 adverse events section.

Sponsor's own description

This trial examined the outcome benefit to patients of adding a new chemotherapy drug combination to the established treatment approach for patients with extracranial Ewing sarcoma, that had not spread from the primary site to other places in the body. The trial randomly assigned patients at the time of study entry to receive established standard treatment with the following 5-drugs: vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide and etoposide. The outcome for patients receiving the standard 5-drug combination was compared to the outcome for patients who received the same 5-drugs with an additional drug, topotecan hydrochloride delivered in a novel combination with vincristine sulfate and cyclophosphamide.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.
    Shulman DS, Klega K, Imamovic-Tuco A, Clapp A, et al · · 2018 · cited 106× · PMID 30131550 · DOI 10.1038/s41416-018-0212-9
  2. Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report.
    Leavey PJ, Laack NN, Krailo MD, Buxton A, et al · · 2021 · cited 84× · PMID 34652968 · DOI 10.1200/jco.21.00358
  3. The Clinical Trials Gap for Adolescents and Young Adults with Cancer: Recent Progress and Conceptual Framework for Continued Research.
    Freyer DR, Seibel NL. · · 2015 · cited 53× · PMID 30613438 · DOI 10.1007/s40124-015-0075-y
  4. Advances in paediatric cancer treatment.
    Saletta F, Seng MS, Lau LM. · · 2014 · cited 50× · PMID 26835334 · DOI 10.3978/j.issn.2224-4336.2014.02.01
  5. Clinical Activity of Pazopanib in Metastatic Extraosseous Ewing Sarcoma.
    Attia S, Okuno SH, Robinson SI, Webber NP, et al · · 2015 · cited 31× · PMID 26266019 · DOI 10.4081/rt.2015.5992
  6. Enhancing Adolescent and Young Adult Oncology Research Within the National Clinical Trials Network: Rationale, Progress, and Emerging Strategies.
    Weiss AR, Nichols CR, Freyer DR. · · 2015 · cited 27× · PMID 26433555 · DOI 10.1053/j.seminoncol.2015.07.012
  7. Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study.
    Harris CJ, Helenowski I, Murphy AJ, Mansfield SA, et al · · 2022 · cited 16× · PMID 33156070 · DOI 10.1097/sla.0000000000004579
  8. Camptothecin-based regimens for treatment of ewing sarcoma: past studies and future directions.
    Wagner L. · · 2011 · cited 15× · PMID 21512587 · DOI 10.1155/2011/957957

Verify or expand the search:

Other trials of Cyclophosphamide

Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01231906.

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