Losartan and Sunitinib for the Treatment of Relapsed or Refractory Osteosarcoma

Active:	Yes
Cancer Type:	Sarcoma	NCT ID:	NCT03900793
Trial Phases:	Phase I	Protocol IDs:	18-2740 (primary) NCI-2019-06119 18-2740.cc
Eligibility:	10 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	UCHealth University of Colorado Hospital
NCI Full Details:	http://clinicaltrials.gov/show/NCT03900793

Summary

This phase I/Ib trial studies the side effects, best dose, and anti-tumor activity of losartan and sunitinib in treating patients with osteosarcoma that has come back (relapsed) or does not respond to treatment (refractory). Losartan and sunitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Objectives

PRIMARY OBJECTIVE:
I. Evaluate the safety, tolerability, and define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the losartan and sunitinib combination in pediatric and adult patients with relapsed or refractory osteosarcoma.

SECONDARY OBJECTIVES:
I. Describe the pharmacokinetics (PK) of losartan when given in combination with sunitinib in pediatric and young adult patients with relapsed or refractory osteosarcoma.
II. Describe the pharmacodynamic (PD) effects of losartan and sunitinib, specifically effects on monocyte migration, plasma CCL2 levels, and changes to the peripheral CCR2+ monocyte population, when given in combination in pediatric and adult patients with relapsed or refractory osteosarcoma.
III. Describe the preliminary antitumor activity of losartan in combination with sunitinib in pediatric and adult patients with relapsed or refractory osteosarcoma.

EXPLORATORY OBJECTIVES:
I. Describe changes to peripheral T cell populations including CD4+, CD8+, and regulatory T cells, which occurs with treatment of losartan and sunitinib.
II. Describe changes to peripheral immune-related cytokines/chemokines such as TGF-beta, IFN-gamma and VEGF with treatment of losartan and sunitinib.
III. Characterize tumor-infiltrating leukocytes, micro-vessel density, and immune-related gene expression in resected pulmonary metastases of patients treated with losartan and sunitinib.

OUTLINE: This is a dose-escalation and dose expansion study of losartan in combination with sunitinib.

Patients receive losartan orally (PO) twice daily (BID) on days 1-42 and sunitinib PO once daily (QD) on days 1-28. Treatment repeats every 42 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography, x-ray imaging, computed tomography (CT) scan, magnetic resonance imaging (MRI), blood sample collection and may undergo positron emission tomography (PET) scan throughout the study.

After completion of treatment, patients are followed up at 30 days, and then periodically for up to 5 years.

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.