Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer (SOLARIS)

STATUS

Recruiting
End date

Jul 5, 2024
participants needed

400
sponsor

Alliance for Clinical Trials in Oncology

Send

Updated on 5 April 2023

See if I qualify

platelet count

cancer

corticosteroids

monoclonal antibodies

measurable disease

fluorouracil

vitamin d

hydrochlorothiazide

major surgery

metastasis

oxaliplatin

neutrophil count

liver metastasis

tumor cells

irinotecan

metastatic colorectal cancer

bevacizumab

rifampin

adjuvant therapy

cancer treatment

solid tumors

lithium

metastatic colorectal adenocarcinoma

folfiri

open biopsy

Summary

This phase III trial studies how well vitamin D3 given with standard chemotherapy and bevacizumab works in treating patients with colorectal cancer that has spread to other parts of the body. Vitamin D3 helps the body use calcium and phosphorus to make strong bones and teeth. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, oxaliplatin, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vitamin D3 with chemotherapy and bevacizumab may work better in shrinking or stabilizing colorectal cancer. It is not yet known whether giving high-dose vitamin D3 in addition to chemotherapy and bevacizumab would extend patients' time without disease compared to the usual approach (chemotherapy and bevacizumab).

Description

PRIMARY OBJECTIVES:

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.

VII. To evaluate the prognostic effect of highest-achieved 25(OH)D levels with PFS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive bevacizumab 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 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.

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

Details

Condition	Colorectal Adenocarcinoma
Treatment	fluorouracil, questionnaire administration, Leucovorin calcium, quality-of-life assessment, bevacizumab, Irinotecan, Oxaliplatin, Cholecalciferol, irinotecan hydrochloride
Clinical Study Identifier	NCT04094688
Sponsor	Alliance for Clinical Trials in Oncology
Last Modified on	5 April 2023

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Histologically confirmed advanced/metastatic colorectal adenocarcinoma for which metastasectomy is not planned
	No known mismatch repair deficiency (dMMR) or high-frequency microsatellite instability (MSI-H) disease
	Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
	No prior systemic treatment for metastatic disease
	Patients may have received prior neoadjuvant or adjuvant chemotherapy and/or chemoradiation. The last course of adjuvant therapy must have been completed > 12 months prior to colorectal cancer recurrence
	Patients may have received prior standard rectal cancer chemoradiation. Previous radiation therapy must have been completed >= 4 weeks prior to registration
	No continuous daily use of vitamin D supplements >= 2,000 IU per day for the 12 months prior to registration. Patients may have had continuous daily use of vitamin D supplements >= 2,000 IU per day if total duration < 12 months in the 12 months prior to registration. Patients may have had continuous daily use of vitamin D supplements < 2,000 IU per day for any duration prior to registration
	Patients must have completed any major surgery or open biopsy >= 4 weeks prior to registration and must have completed any minor surgery or core biopsy >= 1 week prior to registration. (Note: insertion of a vascular access device is not considered major or minor surgery.) Patients must have recovered from the effects of any surgery (e.g. wound is healed, no active infection, no drains, etc.) prior to registration
	Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic, and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =< 14 days prior to registration is required
	Eastern Cooperative Oncology Group (ECOG) performance status: 0-1
	Absolute neutrophil count >= 1,500/mm^3
	Platelet count >= 100,000/mm^3
	Hemoglobin >= 9 g/dL
	Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (Calc.) creatinine clearance (CrCl) > 30 mL/min
	Calcium =< 1.0 x ULN
	Corrected for albumin level if albumin not within institutional limits of normal
	Total bilirubin =< 1.5 x ULN
	If Gilbert's disease, use direct bilirubin instead of total bilirubin; direct bilirubin =< 1.5 x ULN if patient to receive FOLFIRI; direct bilirubin =< 3.0 x ULN if patient to receive leucovorin, infusional fluorouracil, and oxaliplatin (modified [m]FOLFOX6)
	Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
	AST/ALT < 5 x ULN if clearly attributable to liver metastases
	Urine protein to creatinine (UPC) ratio =< 1 mg/dL OR urine protein =< 1+
	If urine protein is above 1, then 24-hour urine must be ≤ 1 g/24 hours
	No "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and have been free of disease for >= 3 years
	No resectable metastatic disease for which potentially curative metastasectomy is
	planned
	No significant history of bleeding events or bleeding diathesis =< 6 months of registration unless the source of bleeding has been resected
	No history of arterial thrombotic events, including, but not limited to, transient ischemic attack, cerebrovascular accident, unstable angina, angina requiring surgical or medical intervention, or myocardial infarction =< 6 months of registration
	No history of clinically significant peripheral artery disease =< 6 months of registration
	No history of uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or greater
	No history of gastrointestinal (GI) perforation =< 12 months of registration except for GI perforation related to a primary colorectal tumor that has since been fully resected
	No history of malabsorption, uncontrolled vomiting or diarrhea, or any other disease significantly affecting GI function that could interfere with the absorption of oral agents
	No history of allergic reaction attributed to compounds of similar chemical or biological composition to the study agents
	No uncontrolled hypertension (defined as blood pressure [BP] > 160/90)
	No serious or non-healing wound, ulcer, or bone fracture
	No uncontrolled intercurrent illness, including, but not limited to, psychiatric illness/social situations that, in the opinion of the treating physician, may increase the risks associated with participation or treatment on the study or may interfere with the conduct of the study or interpretation of the study results
	Patients positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following
	On effective anti-retroviral therapy
	Undetectable HIV viral load by standard clinical assay =< 6 months of registration
	No known pre-existing hypercalcemia =< 6 months of registration
	No known active hyperparathyroid disease or other serious disturbance of calcium metabolism =< 5 years of registration
	No predisposing colonic or small bowel disorders in which symptoms are uncontrolled as indicated by > 3 watery or soft stools daily in patients without a colostomy or ileostomy. Patients with a colostomy or ileostomy are allowed per treating physician discretion
	No symptomatic genitourinary stones =< 12 months of registration
	Patients with treated brain metastases are eligible if follow-up imaging after central nervous system (CNS)-directed therapy shows no evidence of progression >= 28 days prior to registration
	Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required during the first cycle of protocol-specified therapy after registration
	No uncontrolled seizure disorders
	No grade >=2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 regardless of causality
	Patients must be able to swallow oral formulations of the agent
	Concurrent use of supplemental calcium and/or vitamin D is not permitted. Patients must discontinue the supplement(s) at least 7 days prior to registration
	Concurrent use of thiazide diuretics (e.g. hydrochlorothiazide) is not permitted. Patients must discontinue the drug(s) or switch to an alternative anti-hypertensive agent at least 7 days prior to registration
	Chronic concomitant treatment with oral corticosteroids, lithium, phenytoin, quinidine, isoniazid, and/or rifampin are not permitted. Patients must discontinue the agent(s) at least 7 days prior to registration. Short-term use of corticosteroids as antiemetic therapy is acceptable
	Concurrent use of other anti-cancer therapy including chemotherapy, targeted, and/or biological agents is not permitted

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Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer (SOLARIS)