Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

This study is currently recruiting participants.
Verified April 2013 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Thomas E. Witzig, M.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01787409
First received: February 6, 2013
Last updated: April 2, 2013
Last verified: April 2013
  Purpose

This partially randomized clinical trial studies cholecalciferol in improving survival in patients with newly diagnosed cancer with vitamin D insufficiency. Vitamin D replacement may improve tumor response and survival and delay time to treatment in patients with cancer who are vitamin D insufficient


Condition Intervention
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Hepatosplenic T-cell Lymphoma
Male Breast Cancer
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Peripheral T-cell Lymphoma
Stage 0 Chronic Lymphocytic Leukemia
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Chronic Lymphocytic Leukemia
Stage I Colon Cancer
Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
Stage I Rectal Cancer
Stage I Small Lymphocytic Lymphoma
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IIA Colon Cancer
Stage IIA Rectal Cancer
Stage IIB Colon Cancer
Stage IIB Rectal Cancer
Stage IIC Colon Cancer
Stage IIC Rectal Cancer
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IIIA Breast Cancer
Stage IIIA Colon Cancer
Stage IIIA Rectal Cancer
Stage IIIB Breast Cancer
Stage IIIB Colon Cancer
Stage IIIB Rectal Cancer
Stage IIIC Breast Cancer
Stage IIIC Colon Cancer
Stage IIIC Rectal Cancer
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Breast Cancer
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
Dietary Supplement: cholecalciferol
Other: placebo
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Vitamin D Replacement on Tumor Response and Survival Parameters for Vitamin D Insufficient Patients With Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL can improve event free survival (Study I) at 12 months calculated by the exact binomial method. [ Time Frame: Time from study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed at 12 months ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.

  • Percentage of vitamin D insufficient patients with early stage CLL placed on vitamin D replacement can improve the requiring treatment with conventional therapy (Study II) at 36 months calculated by the exact binomial method. [ Time Frame: At 36 months ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.

  • Bio-R response rate (Study II) up to 5 years calculated as the number of patients with Bio-R response divided by the number of evaluable patients. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Bio-R response rate will be calculated as the number of patients with Bio-R response divided by the number of evaluable patients.

  • Percentage of patients who are vitamin D insufficient, defined as a 25 hydroxy-vitamin D (D2 + D3) level less than 25 ng/mL (Study III) up to 5 years calculated by the exact binomial method. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients who are vitamin D insufficient will be estimated. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.


Secondary Outcome Measures:
  • Vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on event-free survival time (Study I) out to 5 years using the method of Kaplan-Meier. [ Time Frame: From study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of event-free survival time in each group will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models.

  • Vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on overall survival time (Study I) out to 5 years using the method of Kaplan-Meier. [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models.

  • Overall response rate (Study II) up to 5 years calculated by the exact binomial 95% confidence intervals. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

  • Time to first treatment (Study II) out to 5 years using the method of Kaplan-Meier. [ Time Frame: From study registration to initiation of anti-CLL therapy, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of time to first treatment will be estimated using the method of Kaplan-Meier.

  • Overall survival (Study II) up to 5 years using the method of Kaplan-Meier. [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Vitamin D replacement in vitamin D insufficient Alaskan Native patients with newly diagnosed CRC or BC on event-free survival time (Study III) out to 5 years using the method of Kaplan-Meier. [ Time Frame: From study registration to progression, initiation of new anti-cancer therapy after completion or cessation of the original treatment, or death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of event-free survival time in for the CRC and BC groups will be estimated using the method of Kaplan-Meier. Differences between the groups within each cancer type will be evaluated using Cox proportional hazard models.

  • Vitamin D replacement in vitamin D insufficient Alaskan Native patients with newly diagnosed CRC or BC on overall survival (Study III) out to 5 years using the method of Kaplan-Meier. [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models.


Estimated Enrollment: 965
Study Start Date: March 2013
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cholecalciferol)
Patients receive cholecalciferol PO once weekly for 12 weeks and then once monthly for a total of 36 months.
Dietary Supplement: cholecalciferol
Given PO
Other Names:
  • Calciol
  • Vitamin D3
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (placebo and cholecalciferol)
Patients receive placebo PO once weekly for 12 weeks and then once monthly for a total of 12 months. Patients then receive cholecalciferol once monthly for up to 24 months.
Dietary Supplement: cholecalciferol
Given PO
Other Names:
  • Calciol
  • Vitamin D3
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated diffuse large B-cell lymphoma (DLBCL) can improve event free survival at 12 months to be equivalent to that of a control population of vitamin D sufficient patients. (Study I) II. To determine if vitamin D replacement in vitamin D insufficient patients with early stage chronic lymphocytic leukemia (CLL) being managed with observation can improve the percentage of patients requiring treatment with conventional therapy at 36 months to that of a control population of vitamin D sufficient patients. (Study II) III. To determine the incidence of vitamin D insufficiency in Alaska Native People with untreated breast cancer and colorectal cancer. (Study III)

SECONDARY OBJECTIVES:

I. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on overall survival. (Study I) II. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on event free survival. (Study I) III. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated T cell lymphoma on event free and overall survival. (Study I) IV. To assess if vitamin D replacement will increase the tumor response rate in Vitamin D insufficient CLL patients. (Study II) V. To assess the effect of vitamin D replacement in vitamin D insufficient Alaskan Native patients with newly diagnosed colorectal cancer (CRC) or breast cancer (BC) on event free and overall survival. (Study III)

TERTIARY OBJECTIVES:

I. To study immune effector cells (lymphocytes, monocytes), serum cytokines, and tumor cells from vitamin D deficient and sufficient patients to learn the effects of vitamin D on both tumor cells and the patient's immune system. (Study I-II) II. To assess the kinetics of vitamin D replacement in vitamin D insufficient Alaskan Native people with CRC or BC. (Study III)

OUTLINE:

STUDY I: Vitamin D sufficient patients receive no intervention. Vitamin D insufficient patients receive cholecalciferol orally (PO) once weekly for 12 weeks and then once monthly for a total of 36 months.

STUDY II: Vitamin D sufficient patients receive no intervention. Vitamin D insufficient patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cholecalciferol PO once weekly for 12 weeks and then once monthly for a total of 36 months.

ARM II: Patients receive placebo PO once weekly for 12 weeks and then once monthly for a total of 12 months. Patients then receive cholecalciferol once monthly for up to 24 months.

STUDY III: Vitamin D sufficient patients receive no intervention. Vitamin D insufficient patients receive cholecalciferol orally (PO) once weekly for 12 weeks and then once monthly for a total of 36 months.

After completion of study treatment, patients are followed up for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed aggressive lymphoma, CLL/small lymphocytic lymphoma (SLL), colorectal cancer, or breast cancer that meets disease specific criteria below:
  • Study 1 - Aggressive lymphoma

    • Newly diagnosed de-novo DLBCL or primary mediastinal B-cell lymphoma that will be treated with an anthracycline-containing regimen (rituximab-cyclophosphamide, doxorubicin hydrochloride, prednisone [R-CHOP] or equivalent); NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; the patient is permitted to participate in any other therapeutic therapy for their disease as long as it does not concern vitamin D; patients can begin their chemotherapy while awaiting vitamin D results and treatment arm assignment or
    • Newly diagnosed untreated peripheral T-cell non-Hodgkin lymphoma (NHL) that will be treated with chemotherapy; NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; this includes the following disease types:

      • Peripheral T cell lymphoma, unspecified
      • Anaplastic large cell lymphoma (T and null cell type)
      • Extranodal NK/T-cell lymphoma, nasal type
      • Enteropathy-type T-cell lymphoma
      • Hepatosplenic T-cell lymphoma
      • Subcutaneous panniculitis-like T-cell lymphoma
      • Angioimmunoblastic T-cell lymphoma
      • Anaplastic large cell lymphoma - primary cutaneous type and
    • Willing to provide tissue for correlative research purposes
  • Study 2 - CLL/SLL

    • Newly diagnosed (< 12 months from registration on this study) CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of:

      • Biopsy-proven small lymphocytic lymphoma
      • Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:

        • Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate size lymphocytes, with < 55% prolymphocytes
        • Immunophenotyping consistent with CLL defined as:

          • The predominant population of lymphocytes share both B-cell antigens (CD19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
          • Dim surface immunoglobulin expression
          • Restricted surface kappa or lambda light chain expression
        • Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
    • Rai stage 0 or 1
    • Previously untreated
    • Asymptomatic with the plan for observation
    • Life expectancy of at least 24 months
    • Willing to provide tissue for correlative research purposes
  • Study 3 - Alaskan Native Medical Center patients with colorectal cancer or breast cancer

    • New cancer of the colon, rectum, or breast
    • =< 12 weeks from the initial biopsy
  • Capable of swallowing intact study medication capsules
  • Serum calcium < 11 mg/dL; note: patients with hypercalcemia can be enrolled after the calcium is corrected with standard of care treatments
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

    • Note: During the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

  • STUDY 2: Unwilling to be randomized to placebo for one year
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01787409

Locations
United States, Iowa
University of Iowa Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Brian K. Link    800-237-1225    brian-link@uiowa.edu   
Principal Investigator: Brian K. Link         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Thomas E. Witzig    507-538-7623    witzig@mayo.edu   
Principal Investigator: Thomas E. Witzig         
United States, Wisconsin
University of Wisconsin Cancer Center Riverview Not yet recruiting
Wisconsin Rapids, Wisconsin, United States, 54494
Contact: Brad S. Kahl    877-405-6866    bsk@medicine.wisc.edu   
Principal Investigator: Brad S. Kahl         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Thomas Witzig Mayo Clinic
  More Information

No publications provided

Responsible Party: Thomas E. Witzig, M.D., Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01787409     History of Changes
Other Study ID Numbers: LS1293, NCI-2013-00037
Study First Received: February 6, 2013
Last Updated: April 2, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms, Male
Breast Neoplasms
Colonic Neoplasms
Rectal Neoplasms
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on April 22, 2014