Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

Anti-Arrhythmia Agents

Antihypertensive Agents

All Drugs and Chemicals

Antineoplastic Agents

Vasoconstrictor Agents

Losartan

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin II Type 1 Receptor Blockers

Angiotensin Receptor Antagonists

Part 1: This is a study escalating doses (Dose level 1-3) of losartan on a continuous daily dosing schedule and sunitinib (escalating on dose level 4) on a daily dosing with 4 weeks on, 2 weeks off. A cycle of therapy is 6 weeks (42 days).Dosing will be performed based on body surface area (BSA). This portion of the study uses a 3+3 design (i.e. cohort sizes of 3 patients for the first and second cohort at each dose level).

Part 2: Once the Maximally Tolerated Dose (MTD) has been determined, 12 patients will enroll to the expansion cohort. These patients will receive the MTD as long as less then 33% of patients experience dose-limiting toxicities.

Losartan will be administered orally daily on days 1-42 (6 weeks) with dose level assignments per Table 1 of the protocol. Dosing will be performed based on weight in kilograms and rounded to the nearest 12.5 mg (half of 25 mg tablet). Dose level 1 dosing will not exceed 50 mg daily and dose levels 2 and 3 dosing will not exceed 100 mg daily. Doses should be taken at approximately the same time daily and patients should fast for \> 4 hours prior to dosing

Sunitinib 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 per Table 1 of the protocol. Doses should be taken at approximately the same time daily.

Natalie Frisbie

Carrye Cost, MD

Thomas Cash, MD

Kelly Faulk, MD

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.

Dose escalation for Phase 1 with dose levels described in Arms and interventions.

Losartan + Sunitinib in Treatment of Osteosarcoma

A Phase I/Ib Study of Losartan in Combination With Sunitinib in the Treatment of Pediatric and Adult Patients With Relapsed or Refractory Osteosarcoma

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

The MTD will be defined as the dose level below that at which 1/3 or 2/6 patients experience DLTs.

The dose that less that 33% of patients experience DLTs.

Determined through a monocyte mitigation assay and reported as a change in chemotactic index from baseline

Assessed by Enzyme Linked Immunosorbent Assay (ELISA).

Stable disease determined according to RECIST 1.1 criteria

Partial response determined according to RECIST 1.1 criteria

Complete response determined according to RECIST 1.1 criteria

Determined according to irRECIST criteria.

Spots Global Cancer Trial Database for Losartan + Sunitinib in Treatment of Osteosarcoma

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