Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colonic Neoplasms

Liver Neoplasms

Neoplastic Processes

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Liver Diseases

Micronutrients

All Drugs and Chemicals

Bone Density Conservation Agents

Hematinics

Vitamins

Herbal and Botanical

Vitamin D

Cholecalciferol

Calcium

Liver Extracts

Calcium, Dietary

Ergocalciferols

Trace Elements

Hormones

Vitamin D3

Calciferol

Cola

Ergocalciferol

Vitamin D2

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.

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.

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.

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

Placebo

Kimmie Ng, MD

Kimmie Ng, MD, MPH

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.

The participant will be given a study drug-dosing diary to keep track of when they take the study drug. The participant will be taking the study drug once every day, for 14 - 28 days, prior to their surgery.

* Run-In Phase: The first 6-12 participants will receive high-dose vitamin D prior to surgery. The number of participants in this phase will be based on the results of the analyzed research samples.
* Randomized Phase: Because no one knows which of the study options is best, the participant will be "randomized" into one of the study groups: high dose vitamin D or standard dose vitamin D.

  * 48 Participants will be randomized to receive high-dose vitamin D or standard-dose vitamin D. Randomization means that the participants are put into a group by chance. Neither the participant nor the research doctor will choose what group the participant will be in. The participant will have an equal chance of getting assigned to each arm (like flipping a coin). The randomized phase will enroll to two groups at the same time:

    * Group A: 24 participants with a recent diagnosis of stage I, II or III colon cancer will be randomized to receive high-dose vitamin D or standard-dose vitamin D.
    * Group B: 24 participants with resectable liver metastases from colon cancer will be randomized to receive high-dose vitamin D or standard-dose vitamin D.

Additional research procedures to be performed on study:

* Blood samples will be collected for research purposes (a little more than 2 teaspoons of blood). The samples will be collected immediately prior to the participant's surgery and used to study the vitamin D receptor and pathway, as well as its relationship to colon cancer. Some of this blood will be stored to be used for future cancer research.
* Tumor tissue will be collected for research purposes at the time of the participant surgery. This tissue will also be used to study the vitamin D receptor and pathway, as well as its relationship to colon cancer. Some of the tumor tissue collected will be sent for use in a separate, but related study. In this study, the participant's tumor will be used to grow cell lines. This means the participant's tumor cells will be multiplied in the lab. These cell lines will be used to study the binding sites in the genes of participants and learn more about vitamin D's role in preventing colon cancer.

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

Study to Identify Transcriptional Targets of Vitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases Receiving Preoperative Vitamin D Supplementation.

Compare VDR binding sites between supplementation arms (high-dose versus standard-dose), between malignant versus adjacent benign colon or liver tissue in those receiving high-dose vitamin D, and between primary colon tumors versus liver metastases in patients exposed to high-dose vitamin D. Laboratory procedures for enriching epithelial cells from the surgical specimen, sonicating cross-linked chromatin, immunoprecipitating VDR-chromatin complexes, and preparing DNA libraries for massively parallel sequencing will be refined.

The goal is to infer direct transcriptional targets of VDR by determining which loci bind VDR and also alter gene expression in response to high-dose vitamin D supplementation. RNA-Seq libraries, prepared from poly(A)+ mRNA and sequenced by Illumina Hi-seq, will be analyzed using Tophat, Cufflinks60 and other new statistical packages to identify consistent differences in transcript levels between tissues exposed to high-dose versus standard-dose vitamin D3 at pre-determined FDRs on the order of 0.01. Stringent tests for statistically significant differences in RNA levels between samples are built into the algorithms for RNA-seq analysis.

Grade of severity in accordance with the NCI-CTCAE version 4.0 guideline

National Cancer Institute (NCI)

Pharmavite LLC

Dana-Farber Cancer Institute

Principal Investigator

Body Weight

Rectal Diseases

DWI-MRI scans at baseline, at 14 days after first administration of chemotherapy and after up to 6 cycles of chemotherapy

Experimental: imaging arm

Oussama Karroum

Sigrid Stroobants

The primary objective of this study is to correlate the percentage change in apparent diffusion coefficient (ADC) between baseline and early therapy (at day 14) with tumor regression grade (TRG) measured in the surgical resection specimen.

This is a prospective, multicenter, single-arm imaging trial. Patients with resectable liver metastases from colorectal cancer (CRC) will undergo Diffusion Weighted Imaging- Magnetic Resonance Imaging (DWI-MRI) scans at least at three separate occasions: at baseline, at 14 days (maximum +/- 1 days deviation is acceptable) after first administration of chemotherapy and finally after up to 6 cycles of chemotherapy (one week prior to surgery).

All patients registered in the study may participate to the test-retest analysis. This analysis required a double baseline scans (called test-retest) to be done on two separate occasions, separated from each other by from one hour to one week but both before start of therapy. The repeated scan at baseline (retest) is optional as it will be used only for the test-retest repeatability analysis.

Dedicated in-house developed software will be used to quantify ADC to assess tumor characteristics and response to therapy.

Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer

Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer Treated With Fluoropyrimidine-based Chemotherapy as Preoperative Treatment

Percentage of ADC changes at day 14 relative to baseline

Tumor regression grade (TRG) in the surgical resection specimen

Repeatability Coefficient from test-retest ADC measurements at baseline

Pre-operative (post-treatment) ADC measurement

Lesion volume (baseline and, if applicable, after 3 cycles and after 6 cycles) using radiological assessment

Histopathological measurements on liver metastases Tumor tissue cellularity/density, Necrosis, Proliferation (ki-67)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Vitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases	NCT02172651	Stage, Colon Ca... Stage I-III Col... Stage IV Colon ...	Vitamin D3 Placebo	18 Years -	Dana-Farber Cancer Institute
Evaluation of Diffusion Weighted Imaging -MRI in Patients With Resectable Liver Metastases From Colorectal Cancer	NCT02355353	Liver Metastase... Colorectal Canc...	Experimental: i...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC

Spots Global Cancer Trial Database for resectable liver metastases