Phase 2 Completed N=139 Randomized Double-blind Treatment

Study of Vitamin D in Untreated Metastatic Colorectal Cancer

Colorectal Cancer

Source: ClinicalTrials.gov NCT01516216 ↗

Enrolled (actual)

139

Serious AEs

63.7%

Results posted

Mar 2022

Primary outcomePrimary: Median Progression-free Survival (PFS) — 11; 13 Months — p=0.07

Summary

This is a prospective, randomized, double-blind phase II trial to evaluate the efficacy and safety of two doses of vitamin D supplementation in combination with standard chemotherapy in participants with previously-untreated metastatic colorectal adenocarcinoma.

Outcome Measures

Outcome	Result	p-value
PRIMARY Median Progression-free Survival (PFS)	11; 13	0.07
SECONDARY Median Overall Survival (OS)	24.3; 24.3	0.43
SECONDARY Objective Response Rate	63; 58	0.27
SECONDARY Grade 3-5 Treatment-Related Neutropenia Toxicity Rate	31; 35	—
SECONDARY Number of Participants With Vitamin D Deficiency at Baseline	39; 48	0.68
SECONDARY Vitamin D Sufficiency Rate	9.8; 71.4	—
SECONDARY Plasma 25-hydroxyvitamin D Levels	18.7; 16.1; 18.7; 32; 18.5; 35.2	—
SECONDARY Hazard Ratio Between Baseline Plasma 25(OH)D Level and PFS	1.00	0.9801
SECONDARY Hazard Ratio Between Baseline Plasma 25(OH)D Levels and OS	0.995	0.7444

Eligibility Criteria

Inclusion Criteria

Histologically confirmed adenocarcinoma of the colon or rectum that is metastatic or locally advanced (unresectable)
Measurable disease
KRAS wild-type and KRAS mutant patients are eligible
No prior systemic treatment for advanced or metastatic colorectal cancer is allowed
No prior radiotherapy to more than 25% of bone marrow
No surgery or major biopsy within 4 weeks of randomization
Paraffin-embedded and/or snap-frozen tumor tissue samples must be available

Exclusion Criteria

Not pregnant or breastfeeding
No prior chemotherapy, systemic therapy or investigational agent
No concurrent use of other anti-cancer therapy
No known brain metastases
No history of other malignancies except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, curatively treated lobular or ductal carcinoma in situ of the breast or other cancer curatively treated with no evidence of disease for more than 3 years prior to randomization
No regular use of vitamin D supplements greater than 2000 IU per day in the past year
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-FU, capecitabine, oxaliplatin, leucovorin, bevacizumab and/or vitamin D3
No significant history of bleeding events, pre-existing bleeding diathesis, coagulopathy or gastrointestinal perforation
No arterial thrombotic events within 6 months of randomization
No serious non-healing wound, ulcer or bone fracture
No history of uncontrolled hypertension
No clinically significant peripheral neuropathy
No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled
No uncontrolled seizure disorder or active neurological disease
No pre-existing hypercalcemia
No known active hyperparathyroid disease
No regular use of thiazide diuretics
No malabsorption, uncontrolled vomiting or diarrhea
No known co-morbid disease that would increase the risk of toxicity
No use of chronic oral corticosteroid therapy or any other therapy that can cause vitamin D depletion
No clinically significant cardiovascular disease
No uncontrolled intercurrent illness
No history of any medical or psychiatric condition or addictive disorder or laboratory abnormality that may increase the risks associated with study participation

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01516216). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.