Study of Vitamin D in Untreated Metastatic Colorectal Cancer

NCT ID: NCT01516216

Last Updated: 2022-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-13
• Study Completion Date: 2019-11-09

Brief Summary

This is a prospective, randomized, double-blind phase II trial to evaluate the efficacy and safety of two doses of vitamin D supplementation in combination with standard chemotherapy in participants with previously-untreated metastatic colorectal adenocarcinoma.

Detailed Description

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.

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Chemotherapy + Standard Dose Vitamin D

FOLFOX-bevacizumab: intravenously on Day 1 (+/- 7 days) of every two-week cycle per institutional standards + 400 IU vitamin D3 orally once daily

Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.

Group Type: ACTIVE_COMPARATOR

FOLFOX + bevacizumab

Intervention Type: DRUG

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Chemotherapy + Higher Dose

FOLFOX-bevacizumab: intravenously on Day 1 (+/- 7 days) of every two-week cycle per institutional standards + 8000 IU daily x 2 weeks as loading dose, followed by 4000 IU daily as maintenance dose.

Participants were treated until disease progression, unacceptable toxicity or withdrawal for other reasons.

Group Type: ACTIVE_COMPARATOR

FOLFOX + bevacizumab

Intervention Type: DRUG

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Interventions

FOLFOX + bevacizumab

Intervention Type: DRUG

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

5-FU (5-fluorouracil); Leucovorin; Oxaliplatin (Eloxatin); Bevacizumab (Avastin)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Kimmie Ng, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kimmie Ng, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Mountain States Tumor Institute- Fruitland

Fruitland, Idaho, United States

Mountain States Tumor Institute - Meridian

Meridian, Idaho, United States

Mountain States Tumor Institute- Nampa

Nampa, Idaho, United States

Mountain States Tumor Institute- Twin Falls

Twin Falls, Idaho, United States

The Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Lowell General Hospital

Lowell, Massachusetts, United States

Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center

Milford, Massachusetts, United States

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Dana-Farber/Brigham and Women's Cancer Center in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, United States

New Hampshire Oncology Hematology-P.A.

Concord, New Hampshire, United States

New Hampshire Oncology Hematology-P.A.

Hooksett, New Hampshire, United States

New Hampshire Oncology Hematology-P.A.

Laconia, New Hampshire, United States

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

Ng K, Nimeiri HS, McCleary NJ, Abrams TA, Yurgelun MB, Cleary JM, Rubinson DA, Schrag D, Miksad R, Bullock AJ, Allen J, Zuckerman D, Chan E, Chan JA, Wolpin BM, Constantine M, Weckstein DJ, Faggen MA, Thomas CA, Kournioti C, Yuan C, Ganser C, Wilkinson B, Mackintosh C, Zheng H, Hollis BW, Meyerhardt JA, Fuchs CS. Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial. JAMA. 2019 Apr 9;321(14):1370-1379. doi: 10.1001/jama.2019.2402.

Reference Type: BACKGROUND

PMID: 30964527 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

11-436

Identifier Type: -

Identifier Source: org_study_id