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A Phase II Clinical Trial of High Dose Vitamin D3 Supplementation in Combination With FOLFOX + Bevacizumab in the 1st Line Treatment of Metastatic Colorectal Cancer

Phase 2
18 Years
79 Years
Not Enrolling
Stage IV Colon Cancer, Stage IV Rectal Cancer

Thank you

Trial Information

A Phase II Clinical Trial of High Dose Vitamin D3 Supplementation in Combination With FOLFOX + Bevacizumab in the 1st Line Treatment of Metastatic Colorectal Cancer


I. To determine the relative rate of metastatic colorectal cancer patients who achieve 25-D3
levels >= 40 ng/ml at 8 weeks, 16 weeks, 24 weeks, and 32 weeks from starting FOLFOX
(leucovorin calcium, fluorouracil, and oxaliplatin) + bevacizumab + high dose vitamin D3
supplementation (cholecalciferol).

II. To estimate the median progression-free survival (PFS) of metastatic colorectal cancer
patients receiving first-line FOLFOX + bevacizumab + high dose vitamin D3 supplementation.


I. To estimate the response rate (RR) and the median overall survival (OS) of metastatic
colorectal cancer patients receiving first-line FOLFOX + bevacizumab + high dose vitamin D3

II. To describe the safety of this combination by capturing all treatment-related toxicity
as per National Cancer Institute-Common Terminology Criteria (NCI-CTC) version 4 guidelines.


Patients receive high-dose cholecalciferol orally (PO) once daily. Patients also receive
bevacizumab intravenously (IV) over 10 minutes, leucovorin calcium IV over 2 hours,
oxaliplatin* IV over 2 hours, and fluorouracil IV continuously over 46 hours once a week.
Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Treatment with oxaliplatin is discontinued after course 8.

After completion of study treatment, patients are followed up at day 30 and then 3 months

Inclusion Criteria:

- Patients should have untreated metastatic colorectal cancer; prior adjuvant
chemotherapy is allowed as long as the development of metastatic disease occurred
more than 6 months from completion of adjuvant treatment

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

- Platelets >= 100,000/mm^3

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Hemoglobin > 9 gm/dl

- Calculated creatinine clearance > 40 ml/min according to the Cockcroft-Gault formula
OR per 24 hour urine collection

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x
institutional upper normal level if no liver metastases and < 5 x upper limit of
normal (ULN) in the setting of liver metastases

- Total bilirubin =< 1.5 x institutional upper normal level

- Albumin >= 2.5 g/dl

- Urine protein:creatinine (UPC) ratio < 1; in the event UPC is > 1, the patient will
require a 24-hr urine protein and will be eligible if 24-hr urine collection has <
1,000 mg protein

- Patients of child-hearing potential must agree to use acceptable contraceptive
methods (e.g., double harrier) during treatment

- Patient or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board-approved
written informed consent form prior to receiving any study-related procedure

- Presence of measurable disease defined as a lesion >= 1 cm by computed tomography
(CT); all sites of disease should be evaluated =< 3 weeks before treatment initiation

- Baseline 25-D3 level of < 40 ng/ml

Exclusion Criteria:

- Patients may not be receiving any other investigational agents that are not included
in this study

- Patients with known brain metastases

- History of other invasive cancers with the exception of the following: a. Curatively
resected or treated non-melanoma skin cancer; b. Curatively treated cervical
carcinoma in situ; c. Other primary solid tumors treated curatively and no treatment
administered >= 2 years before enrollment, and in the investigator opinion, it is
unlikely that there will be a recurrence =< 1 year post enrollment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to oxaliplatin, 5-FU, leucovorin, bevacizumab, and vitamin D3 and other
agents used in study

- History of clinically significant bleeding within 6 months of enrollment

- Clinically significant cardiovascular disease within 12 months prior to enrollment,
including myocardial infarction, unstable angina, grade 2 or greater peripheral
vascular disease, cerebrovascular accident, transient ischemic attack, congestive
heart failure or arrhythmias not controlled by outpatient medication, percutaneous
transluminal coronary angioplasty/stent

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated on this study

- Major surgery within 28 days prior to enrollment or still recovering from prior

- Known dihydropyrimidine dehydrogenase (DpD) deficiency

- History or evidence upon physical examination of central nervous system (CNS) disease
(e.g., primary brain tumor, seizures not controlled with standard medical therapy,
any brain metastases, or history of stroke)

- Serious, nonhealing wound, ulcer, or bone fracture

- Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood
pressure > 95 mmHg despite medications)

- History of arterial thrombosis within the last 12 months

- History of visceral arterial ischemia

- Subjects unwilling or unable to comply with study requirements

- Any condition that in the Investigator's opinion deems the patient an unsuitable
candidate to receive study drug

- Received an investigational agent within 30 clays prior to enrollment

- Treatment with vitamin D replacement with doses exceeding an average of 1000 IU/day
(vitamin D3) within 60 days prior to enrollment

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median PFS

Outcome Description:

The estimated distributions of PFS will be obtained using the product-limit based Kaplan-Meier method. The corresponding 95% confidence intervals for the estimated probability will be computed using the method proposed in Clopper and Pearson.

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Wen Wee Ma

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 176910



Start Date:

August 2010

Completion Date:

June 2012

Related Keywords:

  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms



Roswell Park Cancer InstituteBuffalo, New York  14263