Study of Vitamin D in Untreated Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Kimmie Ng, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01516216
First received: January 13, 2012
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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 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 colorectal cancer.

In this research study, the investigators are comparing standard and higher dose Vitamin D treatment when given in combination with standard treatment for metastatic colorectal cancer. Standard treatment includes the chemotherapy combination of 5-FU, Leucovorin and Oxaliplatin (FOLFOX) with bevacizumab.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: FOLFOX + bevacizumab
Dietary Supplement: Vitamin D
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Phase II Trial of Vitamin D Supplementation in Patients With Previously Untreated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the progression-free survival (PFS) of participants with previously untreated metastatic colorectal cancer randomized to FOLFOX-bevacizumab plus higher-dose vitamin D versus FOLFOX-bevacizumab plus standard-dose vitamin D


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the overall survival (OS) of participants with previously untreated metastatic colorectal cancer randomized to FOLFOX-bevacizumab plus higher-dose vitamin D versus FOLFOX-bevacizumab plus standard-dose vitamin D

  • Objective tumor response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the objective tumor response rate (RR) of participants with previously untreated metastatic colorectal cnacer randomized to FOLFOX-bevacizumab plus higher-dose vitamin D versus FOLFOX-bevacizumab plus standard-dose vitamin D

  • Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To evaluate and compare the toxicity of adding higher-dose vitamin D versus standard-dose vitamin D to FOLFOX-bevacizumab

  • Incidence of vitamin D deficiency [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the incidence of vitamin D deficiency in participants with previously untreated metastatic colorectal cancer

  • Proportion of participants able to achieve and maintain vitamin D sufficiency [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the proportion of participants who are able to achieve and maintain vitamin D sufficiency with higher-dose vitamin D versus standard-dose vitamin D

  • Time course of change in plasma 25-hydroxyvitamin D3 levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the time course of change in plasma 25-hydroxyvitamin D3 [25(OH)D] levles in participants randomized to higher-dose vitamin D versus standard-dose vitamin D

  • Association between plasma 25(OH)D levels and PFS and OS [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the association between plasma 25(OH)D levels and PFS and overall survival


Estimated Enrollment: 120
Study Start Date: March 2012
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Dose Vitamin D
Standard Dose Vitamin D with Bevacizumab and FOLFOX. FOLFOX contains: 5-FU (5-fluorouracil), Leucovorin and Oxaliplatin (Eloxatin).
Drug: FOLFOX + bevacizumab
Given intravenously on Day 1 of every cycle
Other Names:
  • 5-FU (5-fluorouracil)
  • Leucovorin
  • Oxaliplatin (Eloxatin)
  • Bevacizumab (Avastin)
Dietary Supplement: Vitamin D
Standard Dose (400 IU once daily)
Active Comparator: Higher Dose Vitamin D
Higher Dose Vitamin D with Bevacizumab and FOLFOX. FOLFOX contains: 5-FU (5-fluorouracil), Leucovorin and Oxaliplatin (Eloxatin).
Drug: FOLFOX + bevacizumab
Given intravenously on Day 1 of every cycle
Other Names:
  • 5-FU (5-fluorouracil)
  • Leucovorin
  • Oxaliplatin (Eloxatin)
  • Bevacizumab (Avastin)
Dietary Supplement: Vitamin D
Higher Dose (8000 IU once daily for 2 weeks, followed by 4000 IU once daily)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516216

Contacts
Contact: Dana-Farber Cancer Institute, Gastrointestinal Cancer Center, Clinical Research Line 617-632-5960

Locations
United States, Idaho
Mountain States Tumor Institute at St. Luke's Regional Medical Center Recruiting
Boise, Idaho, United States, 83712
Contact: Dan S Zuckerman, MD    208-381-2711      
Principal Investigator: Dan S Zuckerman, MD         
Mountain States Tumor Institute- Fruitland Recruiting
Fruitland, Idaho, United States, 83619
Contact: Dan S Zuckerman, MD    208-381-2711      
Principal Investigator: Dan S Zuckerman, MD         
Mountain States Tumor Institute - Meridian Recruiting
Meridian, Idaho, United States, 83642
Contact: Dan S Zuckerman, MD    208-381-2711      
Principal Investigator: Dan S Zuckerman, MD         
Mountain States Tumor Institute- Nampa Recruiting
Nampa, Idaho, United States, 83686
Contact: Dan S Zuckerman, MD    208-381-2711      
Principal Investigator: Dan S Zuckerman, MD         
Mountain States Tumor Institute- Twin Falls Recruiting
Twin Falls, Idaho, United States, 83301
Contact: Dan S Zuckerman, MD    208-381-2711      
Principal Investigator: Dan S Zuckerman, MD         
United States, Illinois
The Robert H. Lurie Comprehensive Cancer Center of Northwestern University Recruiting
Chicago, Illinois, United States
Contact: Patricia Kartcheske    312-695-1376      
Contact: Halla Nimeiri, MD, MD    312-695-4381      
Principal Investigator: Halla S. Nimeiri, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: GI Research Line    617-632-5960      
Principal Investigator: Kimmie Ng, MD, MPH         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Rebecca Miksad, MD    617-667-7000      
Principal Investigator: Rebecca Miksad, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: David Ryan, MD    617-724-4000      
Principal Investigator: David Ryan, MD         
Lowell General Hospital Recruiting
Lowell, Massachusetts, United States
Contact: Blair Ardman, MD    978-937-6258      
Principal Investigator: Blair Ardman, MD         
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center Recruiting
Milford, Massachusetts, United States
Contact: Michael Constantine, MD    508-488-3700      
Principal Investigator: Michael Constantine, MD         
Newton-Wellesley Hospital Recruiting
Newton, Massachusetts, United States
Contact: Caroline C. Block, MD    617-658-6000      
Principal Investigator: Caroline C. Block, MD         
Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital Recruiting
South Weymouth, Massachusetts, United States
Contact: Rolf Freter, MD    781-624-4800      
Principal Investigator: Rolf Freter, MD         
United States, New Hampshire
New Hampshire Oncology Hematology-P.A. Recruiting
Concord, New Hampshire, United States
Contact: Douglas J. Weckstein, MD    603-224-2556      
Principal Investigator: Douglas J. Weckstein, MD         
New Hampshire Oncology Hematology-P.A. Recruiting
Hooksett, New Hampshire, United States
Contact: Douglas J. Weckstein, MD    603-224-2556      
Principal Investigator: Douglas J. Weckstein, MD         
New Hampshire Oncology Hematology-P.A. Recruiting
Laconia, New Hampshire, United States
Contact: Douglas J. Weckstein, MD    603-224-2556      
Principal Investigator: Douglas J. Weckstein, MD         
Dana-Farber/New Hampshire Oncology-Hematology Recruiting
Londonderry, New Hampshire, United States
Contact: Frederick Briccetti, MD    603-552-9170      
Sub-Investigator: Frederick Briccetti, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Information Program    800-811-8480      
Principal Investigator: Emily Chan, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Kimmie Ng, MD, MPH Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Kimmie Ng, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01516216     History of Changes
Other Study ID Numbers: 11-436
Study First Received: January 13, 2012
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
previously untreated

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Vitamin D
Ergocalciferols
Leucovorin
Vitamins
Bevacizumab
Fluorouracil
Oxaliplatin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014