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Gefitinib, trametinib, disulfiram, and sunitinib added to standard chemotherapy for metastatic osteosarcoma

OstEvo - Osteosarcoma Evolves

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT07477457

This study tests whether adding gefitinib, trametinib, disulfiram, and sunitinib to standard chemotherapy helps people with newly diagnosed metastatic osteosarcoma.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment45 (estimated)
Ages6 Years to 49 Years
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionschemotherapy, gefitinib, trametinib, sunitinib
Locations7 sites (Basking Ridge, New Jersey and 6 other locations)
Trial IDNCT07477457 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial adds four targeted drugs to standard MAP chemotherapy (methotrexate, doxorubicin, cisplatin) for people with newly diagnosed high‑risk metastatic osteosarcoma. Participants in Cohort 1 may enroll before biopsy confirmation and will receive serial research biopsies to study how tumors survive during chemotherapy. Safety of the drug combinations will be monitored alongside measures of tumor response and disease control. The trial is designed to see if the multi‑agent addition improves outcomes compared with historical results from standard chemotherapy alone.

Who should consider this trial

Good fit: Ideal candidates are people with newly diagnosed, high‑risk metastatic osteosarcoma (at least one extrapulmonary metastasis or unresectable metastases) who enroll before day 29 after starting chemotherapy.

Not a fit: Patients without metastatic disease, those who have already received extensive prior chemotherapy beyond early MAP cycles, or those who cannot tolerate additional targeted agents are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding these targeted drugs could improve tumor response and control of metastases, potentially prolonging survival.

How similar studies have performed: This exact combination is largely experimental for osteosarcoma with limited prior success reported in this disease, although some of the individual drugs have shown activity in other cancer types.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Cohort 1 only: Newly Diagnosed, Metastatic Osteosarcoma

1. 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:

   1. Having at least 1 extrapulmonary metastasis, radiographic confirmation of metastasis is adequate, and/or
   2. Unresectable metastases at diagnosis as determined by the investigator
2. 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

1\. 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

1. Patients with newly diagnosed osteosarcoma who are not eligible for Cohorts 1 or 2.
2. Diagnostic biopsy has insufficient material for research.
3. Must be enrolled on MSK IRB 12-245, biospecimen research protocol, with oncologic surgeries planned to be performed at MSK.
4. Orthopedic surgeon assessment is that a research biopsy will not increase the risk of local recurrence.
5. 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

1. Age: Patient must be \> 6 and \< 50 years of age at the time of study enrollment.
2. Disease Status: Metastatic high-risk osteosarcoma with cohort specific criteria above
3. Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky \> 50 for patients \< 16 years of age within 28 days prior to enrollment.
4. Oral Medications: Patients must be able to swallow oral medications as whole tablets/capsule form if a commercially available oral suspension is not available or if tablet dissolution is not stated in the protocol.
5. Organ Function Requirements:

   1. Adequate Hematologic function, defined as:

   i. Absolute neutrophil count \> 250 cells/mcL ii. Platelet count \> 50,000/mcL b. Adequate Renal Function, defined as: i. May use creatinine clearance (estimated or by cystatin C) or radioisotope GFR \> 70 mL/min/1.73m2 or estimated GFR (eGFR) in pediatric patients ii. A serum creatinine based on age/sex (use the Schwartz formula for estimating GFR) c. Adequate Liver Function, defined as: i. Total bilirubin \< 1.5 x ULN for age ii. AST and ALT \< 3 x ULN for age d. Adequate Cardiac Function, defined as: i. No history of congenital prolonged QTc syndrome ii. Correct QT (using Fridericia's correction \[QTcF\]) interval \< 480 msec.

1\. QTcF = QT / RR(0.33), where RR = 60 / heart rate in bpm iii. Left ventricular ejection fraction (LVEF) \> 55 % on echocardiogram or MUGA 6. Assent and Consent: Patients at least 7 years old and less than 18 years old must be willing to assent, and consenting party must consent to research biopsies in Cohort 1. Patients 18 years and older must consent to research biopsies at study entry. All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

7\. Tumor Tissue: Patients must have adequate biopsy tumor tissue, or the patient is willing to undergo a pretreatment research biopsy. A research biopsy following cycles 1 and 2 of treatment done with the thoracotomy procedure will be required. Availability of these paired biopsies will be informative to understanding mechanisms of response and resistance to initial therapy in osteosarcoma and may benefit future patients with this rare cancer.

8\. Concurrent Study Enrollment: Must be enrolled on MSK IRB 12-245, biospecimen research protocol, with oncologic surgeries planned to be performed at MSK.

9\. Pregnancy or Breast Feeding: The effects of the chemotherapeutic agents in OstEvo on the developing human fetus are unknown. For this reason and because OstEvo agents as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 12 months following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately.

10\. Contraception: Women of childbearing potential should adhere to contraception from enrollment through 12 months after completion of systemic chemotherapy administration. Men who are sexually active with women of childbearing potential should adhere to contraception from enrollment through 12 months after completion- of systemic chemotherapy administration 11. Protocol Adherence: Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and evaluations.

Exclusion Criteria:

Cohorts 1 and 2 only:

1. Patients who are receiving any other investigational agents for osteosarcoma therapy are ineligible.
2. Patient with an uncontrolled chronic or active infection or another condition where any component of OstEvo therapy would be contraindicated.
3. 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.
4. Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis-based products would not be a reason for exclusion.
5. Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of oral agents.
6. Patients may not have received prior cardiac irradiation.

Cohort 2 only:

5\. Patients must not have previously been enrolled in OstEvo

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions OsteosarcomaMetastasisGefitinibTrametinibDisulfiramSunitinibMetastatic Osteosarcoma25-257
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.