A Phase I Trial of Cabozantinib (XL184) in Combination With High-dose Ifosfamide in Adults and Children With Relapsed/Refractory Sarcomas (CaIRS Trial)

Children's Hospital of Philadelphia4 sites in 1 country30 target enrollmentOctober 24, 2023

InterventionsCabozantinib

DrugsCabozantinib

Overview

Phase: Phase 1
Intervention: Cabozantinib
Conditions: Not specified
Sponsor: Children's Hospital of Philadelphia
Enrollment: 30
Locations: 4
Primary Endpoint: Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of cabozantinib
Status: Recruiting
Last Updated: 5 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory sarcomas.

Detailed Description

In this study, the investigators will test the activity of cabozantinib in combination with high-dose ifosfamide as targeted therapy for relapsed/refractory sarcomas. Cabozantinib has been shown to inhibit multiple tyrosine kinases, including potent inhibition of kinases, MET and VEGFR2. Therefore, the goal of this study is to see if Cabozantinib can be used to inhibit MET and VEGFR2, or other tyrosine kinases to drive tumor responses in patients.

Registry

clinicaltrials.gov

Start Date

October 24, 2023

End Date

November 1, 2028

Last Updated

5 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Children's Hospital of Philadelphia

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologic diagnosis of any sarcoma, including bone and soft tissue sarcomas. Biopsy from current relapse/progression is highly preferred, though will accept tissue from prior relapse/progression or initial diagnosis with approval from the study Principal Investigator or designee.
•Disease that has progressed on or relapsed after upfront initial therapy, which must have included traditional chemotherapy.
•Evaluable or Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), within 21 days of enrollment.
•Age, within the following parameters by cohort:
•Phase I dose-finding cohort: age 12 to 40 years at the time of enrollment.
•Phase I dose-confirmation cohort: age 5 to \< 12 years at the time of enrollment.
•Body surface area (BSA): \> 0.35 m
•Performance status: Lansky play (\< 16 years of age) or Karnofsky (\> 16 years of age) of ≥ 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories \<
•Prior toxicity: recovery to baseline or grade \< 1, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0), from all acute toxicities, unless adverse events (AE) are clinically non-significant (i.e. alopecia) or controlled on supportive care (i.e. nausea/vomiting, hypothyroidism).
•Able to swallow tablets whole.

Exclusion Criteria

•Radiographic evidence of tumor invading major blood vessels, or endotracheal or endobronchial tumor.
•Radiographic evidence of tumor invading the gastrointestinal tract, including esophagus, stomach, small or large bowel, rectum, or anus.
•Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy or surgery (including radiosurgery) and stable for at least 4 weeks prior to enrollment after radiotherapy or major surgery (i.e. removal or biopsy of brain metastasis). Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment.
•Prior progression/relapse with cabozantinib. Prior therapy with cabozantinib without progression/relapse and prior use of other multi-tyrosine kinase inhibitors is allowed.
•Prior therapy with high-dose ifosfamide (\> 10 g/m2/cycle) at any point.
•Any small molecule inhibitor therapy within 5 half-lives of the drug or 14 days, whichever is shorter, before enrollment.
•Myelosuppressive chemotherapy within 14 days before enrollment.
•Autologous bone marrow transplant (auto-BMT) within 42 days before enrollment.
•Immunotherapy, including chimeric antigen receptor T-cells (CAR-T), within 21 days before enrollment.
•Small port radiation therapy within 14 days before enrollment. Substantial bone marrow radiation (i.e. \> 50% of the pelvis) or craniospinal radiation within 4 weeks before enrollment. Subjects with any clinically relevant ongoing complications from prior radiation therapy should not be treated with cabozantinib until these complications have resolved.

Arms & Interventions

Treatment

Cabozantinib

Intervention: Cabozantinib

Outcomes

Primary Outcomes

Maximum tolerated dose/recommended phase II dose (MTD/RP2D) of cabozantinib

Time Frame: Upon completion of accrual to phase 1 cohort, approximately 1 year

Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0).

Secondary Outcomes

Toxicity profile(Upon completion of trial, approximately 1 year)
Dose-limiting toxicities (DLT)(After two cycles of treatment, average 56 days (one cycle is 28 days))
Antitumor activity Ewing sarcoma(6 months)
Antitumor activity osteosarcoma(6 months)
Antitumor Activity Relapsed/Refractory Sarcomas(6 months)