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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effect of Vitamin D Replacement on Tumor Response and Survival Parameters for Vitamin D Insufficient Patients With Cancer

Brief Summary: 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.

Detailed Summary:

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 assess the percentage of patients requiring treatment with conventional therapy at 36 in months in vitamin D insufficient patients with early stage chronic lymphocytic leukemia (CLL) being managed with observation who undergo vitamin D replacement. (Study II)

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 the effect of vitamin D replacement in vitamin D insufficient CLL patients on Bio-r response rate and overall response rate. (Study II) V. To assess time to treatment and overall survival in vitamin D insufficient CLL patients who received vitamin D replacement. (Study II)

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)

OUTLINE:

  • Event free survival (EFS) (Study I) [ 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 ]
    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.
  • Treatment free status (Study II) [ Time Frame: At 36 months ]
    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.


    • Original Primary Outcome:

    • 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 ]
      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 ]
      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 ]
      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 2

      Current Secondary Outcome:

      • Bio-R response rate (Study II) [ Time Frame: Up to 5 years ]
        Bio-R response rate will be calculated as the number of patients with Bio-R response divided by the number of evaluable patients. If a sufficient number of Bio-R responses are seen, differences in Bio-R rate between the two study groups will be evaluated using Fisher's exact test.
      • EFS time (Study I) [ 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 ]
        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.
      • OS (Study II) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ]
        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. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].
      • Overall response rate (Study II) [ Time Frame: Up to 5 years ]
        Exact binomial 95% confidence intervals for the true overall response rate will be calculated. If a sufficient number of responses are seen, differences in overall response rate between the two study groups will be evaluated using Fisher's exact test.
      • Overall survival (OS) time (Study I) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ]
        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. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].
      • Time to first treatment (Study II) [ Time Frame: From study registration to initiation of anti-CLL therapy, assessed up to 5 years ]
        The distribution of time to first treatment will be estimated using the method of Kaplan-Meier. Differences between the two study groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH [favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)].


      Original Secondary Outcome:

      • 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 ]
        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 ]
        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 ]
        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 ]
        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 ]
        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 ]
        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 ]
        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.


      Information By: Mayo Clinic

      Dates:
      Date Received: February 6, 2013
      Date Started: March 2013
      Date Completion:
      Last Updated: December 20, 2016
      Last Verified: December 2016