Cabozantinib With Ifosfamide in Relapsed/Refractory Sarcomas

NCT06156410 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-019876
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

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.

Conditions

Ewing Sarcoma; Osteosarcoma; Sarcomas

Keywords

relapsed; refractory

Outcome Measures

Primary Outcomes (1)

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

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

  Upon completion of accrual to phase 1 cohort, approximately 1 year

Secondary Outcomes (5)

• 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

Study Arms (1)

Treatment

EXPERIMENTAL

Cabozantinib

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Participants will receive cabozantinib in combination with high-dose ifosfamide for 5 cycles. If still on study therapy the participants will continue with cabozantinib monotherapy for up to 12 total cycles.

Treatment

Eligibility Criteria

• Age: 5 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 m2.
• Performance status: Lansky play (\< 16 years of age) or Karnofsky (\> 16 years of age) of ≥ 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories \< 2.
• 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.
• Hematopoietic function:
• Absolute neutrophil count \> 1,000/uL (without hematopoietic growth factor within the time frame noted below).
• Hemoglobin \> 8 g/dL (without transfusion in the last 7 days).
• Platelets \> 100,000/uL (without transfusion in the last 7 days).
• Renal function:

You may not qualify if:

• 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.
• Major surgery (i.e. abdominal surgery; excluding intracranial surgery as noted above) within 14 days before enrollment. Minor surgeries (including mediport or tunneled catheter placement; excluding needle biopsy for tumor sampling or peripherally inserted central catheter placement) within 10 days before enrollment. Subjects must have documented complete wound healing from major surgery or minor surgery before enrollment.
• Hematopoietic growth factors within 7 days (for short-acting growth factor) or 14 days (for long-acting growth factor) before enrollment.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations. See Table 10 in Section 9.1.4 for components of cabozantinib.
• History of clinically significant hemorrhagic cystitis, defined as grade \> 3 non-infectious cystitis, associated with antineoplastic agents.
• Any medications that are strong CYP3A4 inducers or inhibitors or medications definitely known to cause QTc prolongation.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Children's Hospital Colorado: collaborator
• Alex's Lemonade Stand Foundation: collaborator
• Exelixis: collaborator

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing; Osteosarcoma; Sarcoma; Recurrence

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Theodore Laetsch, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan Donnelly, MPH

CONTACT

267-426-9343; 22ST012@chop.edu

James Robinson, MSW, MPH

CONTACT

215-590-2053; 22ST012@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: December 5, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Participant data will be sent between sites as required by protocol. Sites will all share data with Children's Hospital of Philadelphia and University of Colorado. Data can be accessed and used by the sites for the duration of the study and data analysis period.
• Access Criteria: Must be a Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) approved site of the study.

Locations

US (4)