Cabozantinib With Ifosfamide in Relapsed/Refractory Sarcomas
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age5-40
SponsorChildren's Hospital of Philadelphia
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Phase I dose-finding cohort: age 12 to 40 years at the time of enrollment.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Cabozantinib
DrugParticipants 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 groups
30 Participants
are divided into 1 treatment groupGroup A: TreatmentExperimental treatment 1 intervention
Trial outcomes
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).
Time frame
Upon completion of accrual to phase 1 cohort, approximately 1 yearSecondary outcomes
1
Toxicity profile
Define and describe the toxicity profile (grade 2 and above) of cabozantinib administered in combination with high-dose ifosfamide using Common Terminology Criteria for Adverse Events (CTCAE).
Time frame
Upon completion of trial, approximately 1 year2
Dose-limiting toxicities (DLT)
Define and describe the dose-limiting toxicities (DLT) of cabozantinib administered in combination with high-dose ifosfamide using Common Terminology Criteria for Adverse Events (CTCAE).
Time frame
After two cycles of treatment, average 56 days (one cycle is 28 days)3
Antitumor activity Ewing sarcoma
Evaluate the antitumor activity of cabozantinib administered in combination with high-dose ifosfamide for relapsed/refractory Ewing sarcoma using the Response Criteria for Patients with Solid Tumors (RECIST) scale. Disease progression will be measured periodically while on study.
Time frame
6 months4
Antitumor activity osteosarcoma
Evaluate the antitumor activity of cabozantinib administered in combination with high-dose ifosfamide for relapsed/refractory osteosarcoma using the Response Criteria for Patients with Solid Tumors (RECIST) scale. Disease progression will be measured periodically while on study.
Time frame
6 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Children's Hospital of Philadelphia
Lead sponsor
Children's Hospital Colorado
Collaborator
Alex's Lemonade Stand Foundation
Collaborator
Exelixis
Collaborator
Source ClinicalTrials.gov