NCT07477457

Brief Summary

The researchers are doing this study to find out whether adding gefitinib, trametinib, disulfiram, and sunitinib to standard chemotherapy is a more effective treatment approach for people with osteosarcoma than standard chemotherapy on its own. The researchers will also look at the safety of adding these drugs to standard chemotherapy. The researchers will also use the additional research biopsies from Cohort 1 participants to learn more about how osteosarcoma survives during chemotherapy.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for phase_2

Timeline
22mo left

Started Mar 2026

Geographic Reach
1 country

7 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress10%
Mar 2026Mar 2028

Study Start

First participant enrolled

March 11, 2026

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

March 12, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 17, 2026

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2028

Expected
10 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 11, 2028

Last Updated

March 17, 2026

Status Verified

March 1, 2026

Enrollment Period

2 years

First QC Date

March 12, 2026

Last Update Submit

March 12, 2026

Conditions

Keywords

GefitinibTrametinibDisulfiramSunitinibMetastatic Osteosarcoma25-257

Outcome Measures

Primary Outcomes (2)

  • 12-month progression free survival (PFS) (cohort 1)

    Response will be determined by the investigator and progression will be guided by RECIST 1.1 criteria

    12 months

  • 24-month overall survival (OS) (cohort 2)

    Response will be determined by the investigator and progression will be guided by RECIST 1.1 criteria

    24 months

Study Arms (3)

Newly Diagnosed, Metastatic Osteosarcoma

EXPERIMENTAL

Patient will receive study treatment that includes standard MAP chemotherapy in addition to either gefitinib, trametinib, disulfiram, or sunitinib, or a combination of some of these drugs. Participants will receive the study treatment during 6 treatment Cycles. Each Cycle will last 28 days.

Drug: MethotrexateDrug: DoxorubicinDrug: CisplatinDrug: GefitinibDrug: TrametinibDrug: DisulfiramDrug: Sunitinib

Relapsed, Metastatic Osteosarcoma

EXPERIMENTAL

Patient will receive study treatment that includes standard ifosfamide chemotherapy in addition to either gefitinib, trametinib, disulfiram, or sunitinib, or a combination of some of these drugs. Participants will receive the study treatment during 6 treatment Cycles. Each Cycle will last 21 days.

Drug: GefitinibDrug: TrametinibDrug: DisulfiramDrug: SunitinibDrug: Ifosfamide

Newly Diagnosed Osteosarcoma

EXPERIMENTAL

Research Biopsy only

Procedure: Biopsy

Interventions

Methotrexate 12 g/m\^2 (max dose 20 grams) intravenously over 4 hours or as per institutional standard.

Newly Diagnosed, Metastatic Osteosarcoma

Doxorubicin 37.5 mg/m\^2 intravenously over 15 to 30 minutes or as per institutional standard.

Newly Diagnosed, Metastatic Osteosarcoma

Cisplatin 60 mg/m\^2 intravenously over 4 hours or as per institutional standard.

Newly Diagnosed, Metastatic Osteosarcoma

Gefitinib 400 mg/m\^2/dose (maximum dose 250 mg) orally daily for 14 days (14 doses)

Newly Diagnosed, Metastatic OsteosarcomaRelapsed, Metastatic Osteosarcoma

Trametinib will be dispensed as per institutional standard.

Newly Diagnosed, Metastatic OsteosarcomaRelapsed, Metastatic Osteosarcoma

Disulfiram 250 to 500 mg orally once daily for 14 days

Newly Diagnosed, Metastatic OsteosarcomaRelapsed, Metastatic Osteosarcoma

Sunitinib capsules for under 18 years of age: 15 mg/m\^2/dose (maximum 50 mg) orally once daily x 14 days

Newly Diagnosed, Metastatic OsteosarcomaRelapsed, Metastatic Osteosarcoma

Ifosfamide 2,800 mg/m\^2 intravenously as per institutional standard.

Relapsed, Metastatic Osteosarcoma
BiopsyPROCEDURE

Research biopsy prior to therapy

Newly Diagnosed Osteosarcoma

Eligibility Criteria

Age6 Years - 49 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Cohort 1 only: Newly Diagnosed, Metastatic Osteosarcoma
  • For study entry, the suspected diagnosis of osteosarcoma may be based on clinical judgement. Biopsy confirmation is required for treatment but as this protocol has biologic aims from serial tumor samples, some patients will be enrolled prior to open biopsy. Patients must have a histologic new diagnosis of metastatic high-risk osteosarcoma to start OstEvo systemic therapy. For purposes of this protocol, newly diagnosed, high-risk metastatic osteosarcoma includes:
  • Having at least 1 extrapulmonary metastasis, radiographic confirmation of metastasis is adequate, and/or
  • Unresectable metastases at diagnosis as determined by the investigator
  • Patients may have started systemic conventional chemotherapy but must enroll on this study prior to day 29 of chemotherapy initiation. Having received a single standard MAP cycle (AP x 1 and HDMTX up to 2 times) of chemotherapy prior to enrollment is acceptable
  • Cohort 2 only: Relapsed, Metastatic Osteosarcoma
  • \. Patients must have achieved a radiographically confirmed complete response as determined by the investigator from initial therapy and then relapsed with metastatic high-risk osteosarcoma. No strict size criteria of pulmonary or additional nodules for eligibility are required. For purposes of this protocol, relapsed, metastatic, high-risk osteosarcoma includes:
  • a. First relapse within 24 months of start of first chemotherapy or b. First relapse involving more than one lung nodule, or the lung and any extrapulmonary sites or c. First relapse with pleural disruption at relapse as determined by the investigator which can be determined by CT scan and/or d. Multiply relapsed patients are eligible provided the current relapse is in the context of a radiographically confirmed complete response on the scans preceding the relapse making them potentially eligible for OstEvo 2. Patients may have received only a single cycle of ifosfamide-containing conventional chemotherapy ever and included for the relapse making them eligible for OstEvo, but must enroll on this study prior to day 22 of the first cycle post-relapse
  • Cohort 3 only
  • Patients with newly diagnosed osteosarcoma who are not eligible for Cohorts 1 or 2.
  • Diagnostic biopsy has insufficient material for research.
  • Must be enrolled on MSK IRB 12-245, biospecimen research protocol, with oncologic surgeries planned to be performed at MSK.
  • Orthopedic surgeon assessment is that a research biopsy will not increase the risk of local recurrence.
  • Patients must be willing to assent, and consenting party must consent to the single research biopsy prior to the initiation of chemotherapy. Patients over 18 must consent to research biopsies at study entry.
  • Cohorts 1 and 2 only
  • +12 more criteria

You may not qualify if:

  • Cohorts 1 and 2 only:
  • Patients who are receiving any other investigational agents for osteosarcoma therapy are ineligible.
  • Patient with an uncontrolled chronic or active infection or another condition where any component of OstEvo therapy would be contraindicated.
  • Patients with a history of heart disease including, but not limited to: uncontrolled hypertension within 12 months prior to enrollment; ongoing cardiac dysrhythmias ≥ grade 2 or atrial fibrillation of any grade; unstable angina, symptomatic congestive heart failure, or prior myocardial infarction.
  • Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of oral agents.
  • Patients may not have received prior cardiac irradiation.
  • Cohort 2 only:
  • \. Patients must not have previously been enrolled in OstEvo

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering at Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering at Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering at Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering at Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activites)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering at Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

MeSH Terms

Conditions

OsteosarcomaNeoplasm Metastasis

Interventions

MethotrexateDoxorubicinCisplatinGefitinibtrametinibDisulfiramSunitinibIfosfamideBiopsy

Condition Hierarchy (Ancestors)

Neoplasms, Bone TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsSarcomaNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsQuinazolinesDitiocarbThiocarbamatesCarbamatesAcids, AcyclicCarboxylic AcidsDisulfidesSulfidesSulfur CompoundsPyrrolesAzolesHeterocyclic Compounds, 1-RingIndolesCyclophosphamidePhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsOxazinesCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Damon Reed, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Damon Reed, MD

CONTACT

Asmin Tulpule, MD, PhD

CONTACT

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

March 12, 2026

First Posted

March 17, 2026

Study Start

March 11, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 11, 2028

Last Updated

March 17, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Locations