Vitamin D3 with Chemotherapy and Bevacizumab in Treating Patients with Advanced or Metastatic Colorectal Cancer, SOLARIS Trial

Summary

Objectives

PRIMARY OBJECTIVE:
I. To compare the progression-free survival (PFS) of patients receiving high-dose cholecalciferol (vitamin D3) in combination with standard chemotherapy (leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX] or leucovorin calcium, fluorouracil, and irinotecan hydrochloride [FOLFIRI]) and bevacizumab versus those receiving standard-dose vitamin D3 in combination with standard chemotherapy and bevacizumab.

SECONDARY OBJECTIVES:
I. To compare the objective response rate (ORR) of patients receiving high-dose vitamin D3 in combination with standard chemotherapy + bevacizumab versus those receiving standard-dose vitamin D3 in combination with standard chemotherapy + bevacizumab.
II. To compare the overall survival (OS) of patients receiving high-dose vitamin D3 in combination with standard chemotherapy + bevacizumab versus those receiving standard-dose vitamin D3 in combination with standard chemotherapy + bevacizumab.
III. To evaluate and compare the toxicity of adding high-dose vitamin D3 versus standard-dose vitamin D3 to chemotherapy + bevacizumab.
IV. To assess the influence of diet, body mass index, physical activity, and other lifestyle habits on PFS among patients with locally advanced/metastatic colorectal cancer.
V. To evaluate the incidence of vitamin D3 deficiency in participants with previously untreated metastatic colorectal cancer.
VI. To compare the efficacy of high-dose vitamin D3 versus standard-dose vitamin D3 in subgroups of patients defined by baseline plasma calcifediol (25[OH]D) levels, demographic and clinicopathologic characteristics.
VII. To evaluate the prognostic effect of highest-achieved 25(OH)D levels with PFS.

OTHER OBJECTIVE:
I. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.

EXPLORATORY OBJECTIVES:
I. To evaluate the association between germline variation in vitamin D pathway genes and plasma 25(OH)D levels, response to vitamin D3 supplementation, and patient outcome.
II. To evaluate the impact of high-dose vitamin D3 versus standard-dose vitamin D3 on the plasma angiome, and how the angiome modifies the association between vitamin D3 supplementation and patient outcome.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive bevacizumab (or a Food and Drug Administration [FDA]-approved biosimilar) intravenously (IV) over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV on days 1-3 or irinotecan hydrochloride IV on day 1, leucovorin calcium IV over 90 minutes on day 1, and fluorouracil IV on days 1-3. Patients also receive high-dose cholecalciferol orally (PO) once daily (QD) on days 1-14. Cycles repeat every 14 days for 5 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab (or a FDA-approved biosimilar) and chemotherapy as in Arm I. Patients also receive standard-dose cholecalciferol PO QD on days 1-14. Cycles repeat every 14 days for 5 years in the absence of disease progression or unacceptable toxicity.

All patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo collection of blood on study.

After completion of study treatment, patients are followed every 6 months for 5 years.