Study of Vitamin D in Untreated Metastatic Colorectal Cancer

NCT01516216 | Completed Phase 2 Results DMC

• 1 other identifier: 11-436
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 18

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.

Conditions

Metastatic Colorectal Cancer

Keywords

previously untreated

Outcome Measures

Primary Outcomes (1)

• Median Progression-free Survival (PFS)

  Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Patients who discontinued treatment to pursue potentially curative resection were censored for progression-free survival at the time of surgery. Patients who had not experienced cancer progression or died were censored at their last known follow-up date.

  Disease was evaluated every 4 cycles on treatment and off treatment every 8-16 weeks until PD or non-protocol therapy start if discontinued for reason other than PD. Participants were observed up to 28.5 months with maximum follow-up of 56.7 months.

Secondary Outcomes (8)

• Median Overall Survival (OS)

  Participants were followed for survival by clinic visit or telephone every 3 months post-treatment discontinuation up to 36 months from the date that the last participant was enrolled. Median follow-up was 22.9 months with maximum 56.7 months.

• Objective Response Rate

  Disease was evaluated every 4 cycles on treatment. Median (maximum) treatment duration was 7.3 (28.5) months.

• Grade 3-5 Treatment-Related Neutropenia Toxicity Rate

  AEs were evaluated at day 1 of each cycle on treatment and up to 30 days after the last dose. Maximum treatment duration is 28.5 months with median 7.3 months.

• Number of Participants With Vitamin D Deficiency at Baseline

  Baseline

• Vitamin D Sufficiency Rate

  Plasma samples were collected at 3 timepoints on treatment: first restaging (cycle 5, day 1), second restaging (cycle 9, day 1) and at treatment discontinuation. Median (maximum) treatment duration was 7.3 (28.5) months.

Study Arms (2)

Chemotherapy + Standard Dose Vitamin D

ACTIVE COMPARATOR

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.

Drug: FOLFOX + bevacizumab; Dietary Supplement: Vitamin D

Chemotherapy + Higher Dose

ACTIVE COMPARATOR

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.

Drug: FOLFOX + bevacizumab; Dietary Supplement: Vitamin D

Interventions

FOLFOX + bevacizumab DRUG

Also known as: 5-FU (5-fluorouracil), Leucovorin, Oxaliplatin (Eloxatin), Bevacizumab (Avastin)

Chemotherapy + Higher Dose; Chemotherapy + Standard Dose Vitamin D

Vitamin D DIETARY_SUPPLEMENT

Chemotherapy + Higher Dose; Chemotherapy + Standard Dose Vitamin D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (18)

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

Boise, Idaho, 83712, United States

Location

Mountain States Tumor Institute- Fruitland

Fruitland, Idaho, 83619, United States

Location

Mountain States Tumor Institute - Meridian

Meridian, Idaho, 83642, United States

Location

Mountain States Tumor Institute- Nampa

Nampa, Idaho, 83686, United States

Location

Mountain States Tumor Institute- Twin Falls

Twin Falls, Idaho, 83301, United States

Location

The Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Lowell General Hospital

Lowell, Massachusetts, United States

Location

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

Milford, Massachusetts, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Location

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

South Weymouth, Massachusetts, United States

Location

New Hampshire Oncology Hematology-P.A.

Concord, New Hampshire, United States

Location

New Hampshire Oncology Hematology-P.A.

Hooksett, New Hampshire, United States

Location

New Hampshire Oncology Hematology-P.A.

Laconia, New Hampshire, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 30964527 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folfox protocol; Bevacizumab; Fluorouracil; Leucovorin; Oxaliplatin; Vitamin D

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Kimmie Ng, MD, MPH
• Organization: Dana-Farber Cancer Institute

Kimmie_Ng@dfci.harvard.edu

617-632-4150

Study Officials

• Kimmie Ng, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 24, 2012
• Study Start: April 13, 2012
• Primary Completion: November 9, 2019
• Study Completion: November 9, 2019
• Last Updated: April 26, 2022
• Results First Posted: March 23, 2022

Record last verified: 2022-04

Locations

US (18)