Vitamin D in Patients With Stage I-III Colon Cancer or Resectable Colon Cancer Liver Metastases
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|ClinicalTrials.gov Identifier: NCT02172651|
Recruitment Status : Recruiting
First Posted : June 24, 2014
Last Update Posted : July 28, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Stage, Colon Cancer Stage I-III Colon Cancer Stage IV Colon Cancer With Resectable Liver Metastases||Drug: Vitamin D3 Drug: Placebo||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||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.|
|Actual Study Start Date :||July 14, 2014|
|Estimated Primary Completion Date :||March 31, 2021|
|Estimated Study Completion Date :||May 31, 2021|
Experimental: Vitamin D3 - Blinded Registration
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
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.
Other Name: cholecalciferol (vitamin D3)
Placebo Comparator: Placebo - Blinded Registration
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 placebo capsules once daily for 7 days, followed by one placebo capsule once daily until surgery.
- VDR Binding Sites [ Time Frame: 14 to 28 days ]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.
- RNA transcriptome [ Time Frame: 28 days ]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.
- Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: Baseline, 14 days to 28 days ]Grade of severity in accordance with the NCI-CTCAE version 4.0 guideline
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02172651
|Contact: Kimmie Ng, MD||617-632-5960|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Kimmie Ng, MD 617-632-5960|
|Principal Investigator: Kimmie Ng, MD, MPH|
|Principal Investigator:||Kimmie Ng, MD, MPH||Dana-Farber Cancer Institute|