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)

  Hide Detailed Description

Detailed Description:

Participants will be randomized into one of the study groups-Arm A: Vitamin D (standard dose of 400 IU/day), FOLFOX and Bevacizumab or Arm B: Vitamin D (higher dose of 8000 IU/day for 2 weeks followed by 4000 IU/day), FOLFOX and Bevacizumab.

Study Treatment (A cycle of treatment is 14 days):

Vitamin D

Cycle 1: You will take two capsules of Vitamin D orally, once a day (at the same time), every day. Participants randomized to Arm A will be taking one capsule with 400 IU of Vitamin D and one capsule with placebo (pills with no medicine) so that neither you nor your doctor will know what group you have been assigned to. Participants randomized to Arm B will be taking two capsules of 4000 IU each.

Subsequent Cycles: You will take one capsule orally, once a day (at the same time), every day. Participants randomized to Arm A will be taking one capsule with 400 IU of Vitamin D. Participants randomized to Arm B will be taking one capsule with 4000 IU of Vitamin D.

FOLFOX and bevacizumab

FOLFOX and bevacizumab will be given intravenously (IV, through a vein in your arm) on Day 1 of every cycle for all participants in both Arms A and B. The infusions will take several hours, in addition to your doctor's visit, so you should plan on being in clinic most of the day. Note that the 5-FU is given bolus on day 1 (given as one dose), and is then given as a continuous IV infusion over 2 days. You will need to have a port-a-cath placed. A port-a-cath is a medical device that is placed under the skin. The continuous infusion is delivered by a pump that is inserted into the port-a-cath. The pump will be carried in a pouch that you can hook around your waist. Arrangements will be made for you to have the pump disconnected after 2 days. You may need to return to clinic to have it disconnected.

While on study, the following tests and procedures will be performed:

Cycle 1, Day 1

  • Questions about your health, current medications and any allergies.
  • Physical exam, including vital signs
  • Performance status
  • Routine blood tests to evaluate your health
  • Urine test

Subsequent Cycles, Day 1

  • Questions about your health, current medications, allergies and any side effects you may be having.
  • Physical exam, including vital signs
  • Performance status
  • Routine blood tests to evaluate your health
  • Urine test
  • Review of your study drug diary (please bring with you every visit).

Every 4 cycles (approximately every 8 weeks): An assessment of your tumor by CT scan or MRI.

Additional blood samples for research: Samples will be drawn (a little more than 1 teaspoon of blood) after Cycle 4, Cycle 8 and then every 8 Cycles thereafter.

You will continue to receive treatment as long as your disease does not get worse and you are tolerating the treatment.

End of treatment

  • Questions about your health, current medications and any allergies.
  • Physical exam, including vital signs
  • Performance status
  • Blood tests (routine blood tests to evaluate your health and a blood sample for research)
  • Urine test
  • An assessment of your tumor by CT scan or MRI

After the final dose of the study drug:

You will be followed for safety reasons for 30 days after the last dose of study drug. If you are experiencing side effects, you may continue to be followed until the side effects resolve or until you start another treatment.

If you discontinue study treatment for reasons other than disease progression (for example, side effects), you will be asked to continue to get tumor assessments every 8 - 16 weeks until your disease worsens as demonstrated by a tumor assessment or until you start another therapy to treat your cancer. These assessments may coincide with your routine follow-up, in which case they would not need to be repeated.

We would like to keep track of your medical condition for the rest of your life. We would like to do this by reviewing your medical records and/or by calling you on the telephone every 3 months to see how you are doing. Keeping in touch with you and checking on your condition helps us look at the long-term effects of the research study.

  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 26, 2014