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Randomized Controlled Trial of Neo-adjuvant Progesterone and Vitamin D3 in Women With Large Operable Breast Cancer and Locally Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT01608451
Recruitment Status : Active, not recruiting
First Posted : May 31, 2012
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Dr Rajendra A. Badwe, Tata Memorial Hospital

Tracking Information
First Submitted Date  ICMJE May 22, 2012
First Posted Date  ICMJE May 31, 2012
Last Update Posted Date April 10, 2019
Study Start Date  ICMJE September 2007
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2012)
Disease-free survival [ Time Frame: 5 years ]
Disease-free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01608451 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2012)
Improvements in overall survival, Tumor response [ Time Frame: 5 years ]
Overall Survival
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized Controlled Trial of Neo-adjuvant Progesterone and Vitamin D3 in Women With Large Operable Breast Cancer and Locally Advanced Breast Cancer
Official Title  ICMJE Randomized Controlled Trial of Neo-adjuvant Progesterone and Vitamin D3 in Women With Large Operable Breast Cancer and Locally Advanced Breast Cancer.
Brief Summary

Randomized Controlled Trial of Neoadjuvant Progesterone and Vitamin D3 in women with Large Operable Breast Cancer and Locally Advanced Breast Cancer - A Feasibility Study

Primary Progesterone Timing of surgery during the menstrual cycle and its impact on survival in premenopausal women with operable breast cancer has been extensively researched and reinvestigated by Badwe et al in the randomized clinical trial of 'Primary Progesterone Therapy for Operable Breast Cancer' at Tata Memorial Hospital. The underlying assumption was that the presence of unopposed estrogen (in follicular phase) at the time surgery may be deleterious for survival and that circulating progesterone might counteract this deleterious effect.

Vitamin D3 The most prominent physiological role of hormonally active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol), is regulation of calcium and phosphorous homeostasis and bone metabolism via an intracellular receptor (VDR) which is a member of steroid thyroid hormone super-family of receptors. The VDR receptors are also found in other tissues like breast and prostate.

Vitamin D compounds have also been implicated in promotion of apoptosis in breast cancer cells and evidence suggests that 1,25(OH)2D3 and its synthetic analogues may potentiate responsiveness of breast cancer cells to conventional cytotoxic agents.

Objectives

  1. To see the effect of primary progesterone on survival in women with high risk breast cancer (large operable and locally advanced breast cancer)
  2. To see the effect of Vitamin D3 as an antiproliferative, cytotoxic and apoptotic agent (negative growth regulator) by evaluation of surrogate markers of proliferation and apoptosis.

Inclusion Criteria:

  • Unilateral breast cancer
  • Large operable breast cancer/LOBC (T3N0M0 or T3N1M0) and Locally advanced breast cancer/LABC (T3N1-2M0; T2N2M0)
  • Age <70 years
  • Fit for CT

Exclusion Criteria:

  • Prior Incision Biopsy or Excision Biopsy
  • Metastatic breast cancer
  • Renal failure or deranged Renal Function Test
  • Hypoparathyroidism
  • Pregnant or lactating mothers or women of childbearing age not practicing contraception
  • Patient on any of the following drugs: Magnesium-containing antacids, Digitalis, Phenytoin barbiturates, Thiazide diuretics.
  • Previous history of other cancers except cured skin and cervical carcinoma in situ.

Methodology / Treatment plan

The study drugs (Injectable Progesterone and Vitamin D3) will be tested in the neoadjuvant setting prior to administration of each chemotherapy cycle, in a 2x2 factorial design as below:

Neoadjuvant D3 will be administered as Inj. Arachitol 300,000 IU/ml intramuscular, before each chemotherapy cycle.

Neoadjuvant Progesterone used will be administered as single IM depot injection 500mg 5 days prior to each CT cycle and surgery date.

Primary Objectives Disease-free survival

Secondary Objectives Improvements in overall survival Tumor response

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced Breast Cancer and Large Operable Breast Cancer
Intervention  ICMJE
  • Drug: Cholecalciferol
    Inj Arachitol 300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
    Other Name: IArachitol
  • Drug: Inj. Progesterone
    Injection Progesterone 500 mg deep IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
    Other Name: Inj. Proluton Depot
Study Arms  ICMJE
  • No Intervention: No additional treatment
    No Injection Vit D3 or Injection Progesterone prior to chemotherapy cycle
  • Active Comparator: Inj. Proluton
    Injection Progesterone 500 mg deep IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
    Intervention: Drug: Inj. Progesterone
  • Active Comparator: Inj. Arachitol
    Injection Arachitol (Vitamin D3) 300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
    Intervention: Drug: Cholecalciferol
  • Active Comparator: Inj. Proluton and Inj. Arachitol
    Injection Arachitol (Vitamin D3) 300,000 I.U/ml IM and Injection Progesterone 500 mg deep IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
    Interventions:
    • Drug: Cholecalciferol
    • Drug: Inj. Progesterone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2012)
800
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Unilateral breast cancer
  • Large operable breast cancer/LOBC (T3N0M0 or T3N1M0) and Locally advanced breast cancer/LABC (T3N1-2M0; T2N2M0)
  • Age <70 years
  • Fit for CT

Exclusion Criteria:

  • Prior IB or EB
  • Metastatic breast cancer
  • Renal failure or deranged RFT
  • Hypoparathyroidism
  • Pregnant or lactating mothers or women of childbearing age not practicing contraception
  • Patient on any of the following drugs: Magnesium-containing antacids, Digitalis, Phenytoin barbiturates, Thiazide diuretics.
  • Previous history of other cancers except cured skin and cervical carcinoma in situ.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01608451
Other Study ID Numbers  ICMJE Vitamin D3/377/TMH
TMH project No. 377 ( Other Identifier: Tata Memorial Hospital )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Rajendra A. Badwe, Tata Memorial Hospital
Study Sponsor  ICMJE Tata Memorial Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rajendra A Badwe, MS (Surgery) Tata Memorial Hospital, Ernest Borges Road, Parel, Mumbai 400 012
PRS Account Tata Memorial Hospital
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP