Phase III, Randomized, Double Blind Trial Low Dose Tamoxifen Versus Placebo in Hormone Replacement Therapy (HRT) Users (HOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01579734
Recruitment Status : Active, not recruiting
First Posted : April 18, 2012
Last Update Posted : January 31, 2018
Information provided by (Responsible Party):
European Institute of Oncology

Brief Summary:
The propose of this trial is to assess the effect of low dose tamoxifen for breast cancer prevention in HRT (Hormone Replacement Therapy)users.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Tamoxifen Drug: Placebo Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1884 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: The HOT Study: Hormone Replacement Therapy Opposed by Low Dose Tamoxifen. A Phase III Trial of Breast Cancer Prevention With Low Dose Tamoxifen in HRT Users.
Study Start Date : March 2002
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
1 tablet day for 5 years
Drug: Placebo
1 tablet day for 5 years

Active Comparator: Tamoxifen
Tamoxifen 5 mg, (1 tablet) day for 5 years
Drug: Tamoxifen
1 tablet, 5 mg / day for 5 years
Other Name: Nolvadex, Istubal, Valodex

Primary Outcome Measures :
  1. breast cancer incidence [ Time Frame: 10 years ]
    The primary objective is to assess if tamoxifen at a low dose reduces the incidence of breast cancer in healthy postmenopausal women undergoing or willing to initiate hormone replacement therapy (HRT), including the women who will eventually withdraw HRT during the 5 year intervention period and additional 5 years of follow up.

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: 10 years ]

    Incidence of: other non-invasive breast disorders (i.e., LCIS, atypical hyperplasia) All other cancers (with special reference to endometrial cancer, colorectal cancer, ovarian cancer and melanoma).

    Bone fractures Cardiovascular events Venous thromboembolic events Clinically manifest cataract Overall mortality

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Postmenopausal women candidates to HRT for control of menopausal symptoms or prevention of postmenopausal disorders. women currently undergoing HRT for any duration; (women off HRT for 1 year or longer are considered de novo users);
  • negative bilateral mammography (within the last 6 months);
  • written informed consent.

Exclusion Criteria:

Any type of malignancy, with the exclusion of CIN and non-melanoma skin cancer;

  • active proliferative disorders of the endometrium such as atypical hyperplasia, history of active endometriosis, unresected polyps, symptomatic myomata;
  • alterations of metabolic, liver, renal and cardiac grade 2 function (NCI criteria grade 2 or higher);
  • any type of retinal disorders, severe cataract and glaucoma;
  • presence of significant risk factors for venous events, including immobilization within the last 3 months for longer than 2 weeks following surgery or trauma, history of estrogen-associated and "sine causa" superficial phlebitis, deep venous thrombophlebitis or other significant VTE (pulmonary embolism, stroke, etc.);
  • use of tamoxifen, raloxifene or other SERMs within the last 4 weeks;
  • anticoagulant therapy in progress (heparin or dicoumarol);
  • active infections;
  • severe psychiatric disorders or inability to comply to the protocol procedures; any other factor that at the investigator's discretion contraindicates the use of either tamoxifen or HRT.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01579734

European Institute of Oncology
Milan, Italy, 20141
Sponsors and Collaborators
European Institute of Oncology
Study Chair: Umberto Veronesi, MD European Institute of Oncology

Responsible Party: European Institute of Oncology Identifier: NCT01579734     History of Changes
Other Study ID Numbers: IEO S51/200
First Posted: April 18, 2012    Key Record Dates
Last Update Posted: January 31, 2018
Last Verified: December 2017

Keywords provided by European Institute of Oncology:
breast cancer chemoprevention postmenopause

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogen Antagonists
Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents