Losartan + Sunitinib in Treatment of Osteosarcoma
ConditionOsteosarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age10+
SponsorUniversity of Colorado, Denver
About this trial
This study is a Phase 1/1b clinical trial that aims to determine the Maximally Tolerated Dose of Losartan and Sunitinib Combination Therapy. Patients will first be accrued to the Dose Escalation phase of the study, using a 3+3 design. Medication dosages will increase until a maximally tolerated dose is found. Patients will then be accrued to the Dose Expansion phase of the trial, where efficacy of pre-determined dose will be preliminarily assessed.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1. Provision to sign and date the consent form (if individual is a minor, provision of a parent or legal guardian to sign and date the consent form and provision of individual to provide assent for study).
Patients with surface or periosteal osteosarcoma are not eligible.
Patients with active CNS metastasis are not eligible. Previously treated CNS metastases which occurred 3 months or more prior, without evidence of active recurrence, are acceptable.
Dose Escalation (Part A): Patients must have measurable or evaluable disease.
Disqualifiers
Peripheral absolute neutrophil count (ANC) ≥ 750/mm3
Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 OR a serum creatinine based on age/gender.
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
Trial design
Design model
Sequential
Treatments tested in this trial
Losartan
DrugLosartan will be administered orally daily on days 1-42 (6 weeks) of each 42-day cycle according to assigned dose level. Dosing will be performed based on weight in kilograms and rounded to the nearest 12.5 mg (half of 25 mg tablet). Dose Levels 1 and 2 are closed to enrollment. Dose level 1 does not exceed 50mg daily. Dose level 2 does not exceed 100mg daily. Dose levels 3 and 4 do not exceed 150mg total daily. Doses should be taken at approximately the same time daily and patients should fast for at least 4 hours prior to and 1 hour after the morning dose. No fasting is required for evening dose.
Sunitinib
DrugSunitinib will be administered orally daily on days 1-28 (4 weeks), followed by 14-day rest period (2 weeks). Dosing will be performed based on body surface area (BSA) in mg/m2. Sunitinib is given as capsules or liquid formulation. Doses should be taken at approximately the same time daily.
Treatment groups
41 Participants
are divided into 1 treatment groupGroup A: Dose Escalation and ExpansionExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Assessment of Dose-Limiting Toxicities of Losartan and Sunitinib Combination
Assessment of Dose-Limiting Toxicities (DLTs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5 to assess the safety of the combination
Time frame
Beginning of study to end of study, up to 4 years2
Maximally Tolerated Dose of Losartan and Sunitinib
The MTD will be defined as the dose level below that at which 1/3 or 2/6 patients experience DLTs.
Time frame
Beginning of study to end of study, up to 4 years3
Recommended Phase 2 Dose of Losartan and Sunitinib
The dose than less that 33% of patients experience DLTs.
Time frame
Beginning of study to end of study, up to 4 yearsSecondary outcomes
1
Pharmacokinetics of Losartan and Sunitinib in Pediatric and Adult Patients: Maximum Peak Concentration
Determined through blood samples
Time frame
Days 1, 15, and 29 of Cycle 1 (Cycle length is 42 days)2
Pharmacokinetics of Losartan and Sunitinib in Pediatric and Adult Patients: Time to Peak Concentration
Determined through blood samples
Time frame
Days 1, 15, and 29 of Cycle 1 (Cycle length is 42 days)3
Pharmacodynamics of Losartan and Sunitinib in Pediatric and Adult Patients: CCL2-Mediated Chemotactic Index
Determined through a monocyte mitigation assay and reported as a change in chemotactic index from baseline
Time frame
Beginning of study to end of treatment, up to 2 years (up to 17 cycles and cycle length is 42 days)4
Pharmacodynamics of Losartan and Sunitinib in Pediatric and Adult Patients: Plasma CCL2 Levels
Assessed by Enzyme Linked Immunosorbent Assay (ELISA).
Time frame
Beginning of study to end of treatment, up to 2 years (up to 17 cycles and cycle length is 42 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
Cancer League of Colorado
Collaborator
Colorado State University
Collaborator
Swim Across America
Collaborator
Source ClinicalTrials.gov