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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Tata Memorial Hospital
Sponsor:
Information provided by (Responsible Party):
Dr Rajendra A. Badwe, Tata Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01608451
First received: May 22, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Locally Advanced Breast Cancer and Large Operable Breast Cancer
Drug: Cholecalciferol
Drug: Inj. Progesterone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Neo-adjuvant Progesterone and Vitamin D3 in Women With Large Operable Breast Cancer and Locally Advanced Breast Cancer.

Resource links provided by NLM:


Further study details as provided by Tata Memorial Hospital:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Disease-free survival


Secondary Outcome Measures:
  • Improvements in overall survival, Tumor response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Overall Survival


Estimated Enrollment: 800
Study Start Date: September 2007
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Drug: Cholecalciferol
300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
Other Name: I
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.
Drug: Cholecalciferol
300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
Other Name: I
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01608451

Contacts
Contact: Dr. Rajendra A Badwe, MS +91-022-2417-7000 ext 7299 badwera@gmail.com

Locations
India
Tata Memorial Hospital Recruiting
Mumbai, Maharashtra, India, 400012
Principal Investigator: Rajendra A Badwe, MS (Surgery)         
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
Principal Investigator: Rajendra A Badwe, MS (Surgery) Tata Memorial Hospital, Ernest Borges Road, Parel, Mumbai 400 012
  More Information

Publications:

Responsible Party: Dr Rajendra A. Badwe, Principal Investigator, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT01608451     History of Changes
Other Study ID Numbers: Vitamin D3/377/TMH, TMH project No. 377
Study First Received: May 22, 2012
Last Updated: June 23, 2014
Health Authority: India: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cholecalciferol
Ergocalciferols
Progesterone
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Progestins

ClinicalTrials.gov processed this record on October 22, 2014