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Locally Advanced Breast Cancer and Large Operable Breast CancerPhase 3NCT01608451

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

A Phase 3 study testing Cholecalciferol and Inj. Progesterone in people with Locally Advanced Breast Cancer and Large Operable Breast Cancer, run by Tata Memorial Hospital at 1 site in India.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Cholecalciferol and Inj. Progesterone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
800 participants
Where
1 siteIndia
Study dates
Sep 2007to 20 Aug 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

India1 site
  • Tata Memorial Hospital

    Mumbai, Maharashtra, 400012

Other trials in India

About this study

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

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.

Read more

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

Being tested
Cholecalciferol, Inj. Progesterone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CholecalciferolDrug

    Also called IArachitol

    Inj Arachitol 300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.

  • Inj. ProgesteroneDrug

    Also called Inj. Proluton Depot

    Injection Progesterone 500 mg deep IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.

Study groups in NCT01608451
Study groupRoleWhat they receive
No additional treatmentNo interventionNo Injection Vit D3 or Injection Progesterone prior to chemotherapy cycle
Inj. ProlutonActive comparatorInjection Progesterone 500 mg deep IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
Receives: Drug: Inj. Progesterone
Inj. ArachitolActive comparatorInjection Arachitol (Vitamin D3) 300,000 I.U/ml IM before each cycle of NACT (for total 4 cycles) and one injection before surgery.
Receives: Drug: Cholecalciferol
Inj. Proluton and Inj. ArachitolActive comparatorInjection 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.
Receives: Drug: Cholecalciferol; Drug: Inj. Progesterone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-free survival

    Disease-free survival

    Measured: 5 years

Secondary outcomes (1)
  1. Improvements in overall survival, Tumor response

    Overall Survival

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2012 (estimated)
  2. Study startSep 2007
  3. Primary completion20 Aug 2021
  4. Study completion20 Aug 2021

Why it stopped: Slow accrual implies that clinical questions being questioned have lost its significance.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
800 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01608451
Sponsor's protocol ID
Vitamin D3/377/TMH
Other IDs
TMH project No. 377
Status last verified
Apr 2022
First submitted
22 May 2012
Last updated
2 May 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Hrushesky WJ, Bluming AZ, Gruber SA, Sothern RB. Menstrual influence on surgical cure of breast cancer. Lancet. 1989 Oct 21;2(8669):949-52. doi: 10.1016/s0140-6736(89)90956-2.

    PubMed 2571865
  • Badwe RA, Gregory WM, Chaudary MA, Richards MA, Bentley AE, Rubens RD, Fentiman IS. Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer. Lancet. 1991 May 25;337(8752):1261-4. doi: 10.1016/0140-6736(91)92927-t.

    PubMed 1674070
  • Heer K, Kumar H, Speirs V, Greenman J, Drew PJ, Fox JN, Carleton PJ, Monson JR, Kerin MJ. Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery? Br J Cancer. 1998 Nov;78(9):1203-7. doi: 10.1038/bjc.1998.655.

    PubMed 9820181
  • Senie RT, Rosen PP, Rhodes P, Lesser ML. Timing of breast cancer excision during the menstrual cycle influences duration of disease-free survival. Ann Intern Med. 1991 Sep 1;115(5):337-42. doi: 10.7326/0003-4819-115-5-337.

    PubMed 1863022
  • Mathiasen IS, Colston KW, Binderup L. EB 1089, a novel vitamin D analogue, has strong antiproliferative and differentiation inducing effects on cancer cells. J Steroid Biochem Mol Biol. 1993 Sep;46(3):365-71. doi: 10.1016/0960-0760(93)90226-m.

    PubMed 9831485
  • Welsh J. Vitamin D and breast cancer: insights from animal models. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1721S-4S. doi: 10.1093/ajcn/80.6.1721S.

    PubMed 15585794
  • Gulliford T, English J, Colston KW, Menday P, Moller S, Coombes RC. A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer. Br J Cancer. 1998 Jul;78(1):6-13. doi: 10.1038/bjc.1998.434.

    PubMed 9662243
  • Wang Q, Lee D, Sysounthone V, Chandraratna RAS, Christakos S, Korah R, Wieder R. 1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat. 2001 May;67(2):157-68. doi: 10.1023/a:1010643323268.

    PubMed 11519864
  • Narvaez CJ, Zinser G, Welsh J. Functions of 1alpha,25-dihydroxyvitamin D(3) in mammary gland: from normal development to breast cancer. Steroids. 2001 Mar-May;66(3-5):301-8. doi: 10.1016/s0039-128x(00)00202-6.

    PubMed 11179738
  • James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol. 1996 Jul;58(4):395-401. doi: 10.1016/0960-0760(96)00048-9.

    PubMed 8903423
  • Vink-van Wijngaarden T, Pols HA, Buurman CJ, van den Bemd GJ, Dorssers LC, Birkenhager JC, van Leeuwen JP. Inhibition of breast cancer cell growth by combined treatment with vitamin D3 analogues and tamoxifen. Cancer Res. 1994 Nov 1;54(21):5711-7.

    PubMed 7923220
  • Sundaram S, Gewirtz DA. The vitamin D3 analog EB 1089 enhances the response of human breast tumor cells to radiation. Radiat Res. 1999 Nov;152(5):479-86.

    PubMed 10521924
  • Chaudhry M, Sundaram S, Gennings C, Carter H, Gewirtz DA. The vitamin D3 analog, ILX-23-7553, enhances the response to adriamycin and irradiation in MCF-7 breast tumor cells. Cancer Chemother Pharmacol. 2001 May;47(5):429-36. doi: 10.1007/s002800000251.

    PubMed 11391859
  • Sundaram S, Sea A, Feldman S, Strawbridge R, Hoopes PJ, Demidenko E, Binderup L, Gewirtz DA. The combination of a potent vitamin D3 analog, EB 1089, with ionizing radiation reduces tumor growth and induces apoptosis of MCF-7 breast tumor xenografts in nude mice. Clin Cancer Res. 2003 Jun;9(6):2350-6.

    PubMed 12796405
  • Zinser GM, Tribble E, Valrance M, Urben CM, Knutson JC, Mazess RB, Strugnell SA, Welsh J. 1,24(S)-dihydroxyvitamin D2, an endogenous vitamin D2 metabolite, inhibits growth of breast cancer cells and tumors. Anticancer Res. 2005 Jan-Feb;25(1A):235-41.

    PubMed 15816543

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cholecalciferol and Inj. Progesterone in people with Locally Advanced Breast Cancer and Large Operable Breast Cancer, run by Tata Memorial Hospital at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow accrual implies that clinical questions being questioned have lost its significance.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01608451, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2022.

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