Vitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases

NCT02172651 | Recruiting Early Phase 1 DMC

• 2 other identifiers: 14-091P50CA127003-06A1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to learn more about the vitamin D receptor and its relationship to colon cancer. The Vitamin D receptor is found in colon cancer cells. When Vitamin D binds to the receptor in the cancer cells, it may stop cancer cells from growing abnormally and may cause cancer cell death. Vitamin D has been used in other research studies and information from those other research studies suggests that Vitamin D may help in the treatment of colon cancer. Participants will receive either high-dose vitamin D or standard-dose vitamin D. The study drug will be given 14-28 days prior to your surgery. The number of days will depend on when the surgery is scheduled.

Conditions

Stage, Colon Cancer; Stage I-III Colon Cancer; Stage IV Colon Cancer With Resectable Liver Metastases

Keywords

Vitamin D; Stage I-III colon cancer; Stage IV colon cancer; Resectable liver metastases

Outcome Measures

Primary Outcomes (1)

• VDR Binding Sites

  For patients undergoing primary colon resection, the goal is to identify VDR binding sites in malignant and normal colonic tissue collected from colon cancer patients treated with high-dose vitamin D3 versus placebo. ChIP-Seq will be performed on frozen tumor tissue and adjacent normal colon tissue to determine VDR binding sites, which will be compared between the high-dose vitamin D and placebo arms, and between malignant tumor and normal colon tissue.

  14 to 28 days

Secondary Outcomes (2)

• Changes in TME

  14 to 28 days

• Number of Participants with Serious and Non-Serious Adverse Events

  Baseline, 14 days to 28 days

Study Arms (2)

Vitamin D3 - Blinded Registration

EXPERIMENTAL

One capsule of vitamin D3 10,000 IU orally once daily for 14 days until the date of surgery. To allow for some flexibility in the scheduling of surgery, patients can be treated with preoperative vitamin D3 for up to 28 days. On the morning of surgery, prior to operating, a second blood sample will be collected for follow-up 25(OH)D, calcium, and albumin determination. Colon and liver resection will occur per institutional standards of care, and malignant and adjacent benign tissue will be collected for the laboratory endpoints described in this protocol.

Drug: Vitamin D3

Placebo - Blinded Registration

PLACEBO COMPARATOR

One placebo capsule orally once daily for 14 days until the date of surgery. To allow for some flexibility in the scheduling of surgery, patients can be treated with preoperative placebo for up to 28 days. On the morning of surgery, prior to operating, a second blood sample will be collected for follow-up 25(OH)D, calcium, and albumin determination. Colon and liver resection will occur per institutional standards of care, and malignant and adjacent benign tissue will be collected for the laboratory endpoints described in this protocol.

Drug: Placebo

Interventions

Vitamin D3 DRUG

Take five 10,000 IU capsules (total 50,000 IU) once daily for 7 days, followed by one 10,000 IU capsule once daily until surgery.

Also known as: cholecalciferol (vitamin D3)

Vitamin D3 - Blinded Registration

Placebo DRUG

Take five placebo capsules once daily for 7 days, followed by one placebo capsule once daily until surgery.

Placebo - Blinded Registration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically confirmed adenocarcinoma of the colon that is localized, with no evidence of distant metastasis (stage I, II, or III), and for which surgical resection of the primary tumor is being planned;
• Participants must have histologically or cytologically confirmed adenocarcinoma of the colon with resectable liver metastases for which liver resection is being planned.
• No prior radiation therapy or systemic treatment is allowed for patients undergoing resection of stage I, II, or III colon cancer.
• Prior systemic treatment or radiation therapy is allowed for patients with resectable liver metastases.
• The last dose of chemotherapy or radiation must have been administered at least 4 weeks prior to liver surgery.
• The last dose of bevacizumab must have been administered at least 6 weeks prior to liver resection.
• Age ≥18 years.
• ECOG performance status ≤ 1 (see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• Total bilirubin ≤1.5× institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, or \<5x ULN if clearly attributable to liver metastases
• Serum calcium (corrected for albumin level) ≤ 1x institutional ULN
• Serum creatinine within normal institutional limits or creatinine clearance ≥60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
• Participants on full-dose anticoagulation are eligible if the following criteria are met:

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Prior systemic therapy, radiotherapy, or investigational agent in participants undergoing surgery for stage I, II, or III colon cancer.
• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for bevacizumab) of liver resection.
• Concurrent use of other anti-cancer therapy, including chemotherapy agents, targeted agents, biological agents, immunotherapy, or investigational agents not otherwise specified in this protocol.
• Inability to swallow pills.
• History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease significantly affecting gastrointestinal function that could interfere with absorption of oral medications.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin D.
• Regular use of supplemental vitamin D totaling ≥ 2,000 IU/day in the past year.
• Use of supplemental vitamin D or supplements containing vitamin D beyond the protocol-prescribed study treatment is not allowed during the treatment period of this clinical trial.
• In order to maintain blinding, vitamin D levels should not be routinely checked at screening or during the study by the treating investigator. Vitamin D levels will be assayed only as part of the research blood samples collected during the study. If there are concerns related to a participant's vitamin D status, the lead Principal Investigator should be contacted for further discussion.
• Use of chronic oral corticosteroid therapy, lithium, phenytoin, quinidine, isoniazid, and/or rifampin (all of which can cause vitamin D depletion). Short-term use of corticosteroids as anti-emetic therapy for chemotherapy is permitted.
• Regular use of thiazide diuretics (i.e., hydrochlorothiazide), which can lead to hypercalcemia, and unwillingness or inability to discontinue or switch to an alternative anti-hypertensive agent.
• Pre-existing hypercalcemia (defined as baseline serum calcium above the institutional ULN, corrected for albumin level if albumin is not within institutional limits of normal).
• \-- The use of supplemental calcium or supplements containing calcium is prohibited during the treatment period of this clinical trial.
• Known active hyperparathyroid disease or other serious disturbance of calcium metabolism in the past 5 years.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Pharmavite LLC: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Kimmie Ng, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimmie Ng, MD

CONTACT

617-632-5960

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2014
• First Posted: June 24, 2014
• Study Start: July 14, 2014
• Primary Completion: April 15, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)