Antiestrogen vs Aromatase Inhibitor After Adjuvant Chemotherapy for Breast Cancer

March 28, 2012 updated by: Japan Breast Cancer Research Network

Antiestrogen vs Aromatase Inhibitor After Chemotherapy for Adjuvant Setting: Efficacy of Endocrine Therapy After Chemotherapy in Postoperative Adjuvant Therapy for Breast Cancer

To investigate the benefit of postoperative adjuvant therapy using sequential administration of the hormone, toremifene citrate (TOR) or anastrozole (ANA), after chemotherapy in breast cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

To investigate the benefit of postoperative adjuvant therapy using sequential administration of the hormone, toremifene citrate (TOR) or anastrozole (ANA), after chemotherapy in breast cancer.

TOR is reported to be as effective, or more effective, than TAM on both DFS and OS for postoperative adjuvant therapy. The incidence rate and severity of its adverse effects are similar to those of TAM as shown in two clinical trials, the Finnish Breast Cancer Group (FBCG) and the International Breast Cancer Study Group (IBCSG). Although no significant difference was observed in these trials, other studies report that TOR produced a lower number of thromboembolism events compared with TAM, a undesirable side effect seen in patients treated with TAM. Additionally, compared with TAM, TOR showed less endometrial hypertrophy which is induced by estrogen.

Endometrial cancer remains one of the significant problems associated with TAM. A TAM metabolite binds to DNA and forms DNA adducts which damage cells. It is reported that TAM has an expanded ability to form DNA adducts compared with TOR in vitro. A recent study compared endometrial cells collected from patients in which TAM or TOR had been administered. The k-ras gene mutation was investigated in these cases, and it showed that TAM held a higher frequency of gene mutation. Although we still need to discuss whether or not k-ras mutation is directly related to the development of endometrial cancer, TAM seems to have a higher risk of inducing cancer compared with TOR.

In the IBCSG14-93 trials, two chemotherapy protocols were studied subsequent to administration of TOR. They were doxorubicin and cyclophosphamide (AC) and cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). These two chemotherapy protocols were administered in the following sequence: AC four times followed by CMF three times after administration of TOR. The findings revealed that in estrogen-receptor (ER) positive cases, DFS equaled 73% in the TOR group, 65% in the TAM group; hormone receptor (HR=0.80 (0.57-1.11); P=0.18). OS was found to total 88% in the TOR group, 84% in the TAM group; HR=0.78 (0.48-1.27); p=0.32). Although there was no significant difference in two groups, the TOR group has showed somewhat improved survival.

Based on the information provided above, we consider TAM and TOR to have similar efficacy with less adverse effects, and this trial will compare the two drugs, TOR and ANA.

Study Type

Interventional

Enrollment (Anticipated)

240

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Fukuoka, Japan, 815-8588
        • Kyushu Central Hospital
      • Hirakata, Japan, 573-1191
        • Kansai Medical University Hirakata Hospital
      • Hirosaki, Japan, 036-8563
        • Hirosaki University Hospital
      • Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital
      • Matsudo, Japan, 270-2253
        • Shinyahashiradai Hospital
      • Tokyo, Japan, 113-8655
        • The University of Tokyo Hospital
      • Tokyo, Japan, 141-0032
        • Nagumo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Written consent obtained for study participation.
  • Breast cancer diagnosed histologically with a breast removed or preserved.
  • Positive ER or PR testing by immunohistochemistry (IHC), enzyme immunoassay (EIA) and who meet the criteria of each institution.
  • HER2 evaluation.
  • Patient Status (PS): 0 or 1.
  • Fully functional heart, liver, kidneys, and bone marrow.
  • More than one year since last menstruation or tested postmenopausal from estradiol (E2) and follicle-stimulating hormone (FSH) levels based on evaluation standard of each institution.
  • Expected to live for at least three months (or longer) after study commencement.

Exclusion Criteria:

  • Pregnant or breast feeding.
  • Bilateral or inflammatory breast cancer.
  • Multiple cancers.
  • Life-threatening metastases.
  • History of serious hypersensitivity.
  • Judged ineligible for the study by the study doctor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Fareston
Toremifene citrate: 40-mg tablets by mouth once daily.
Drug: Toremifene citrate
Toremifene citrate: 40-mg tablets by mouth once daily.
Other Names:
  • Fareston
Other: Arimidex
Anastrozole: 1-mg tablets by mouth once daily.
Drug: Anastrozole
Anastrozole: 1-mg tablets by mouth once daily.
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recurrence-free rate
Time Frame: The observation period is designated as 10 years from the commencement of treatment.
The observation period is designated as 10 years from the commencement of treatment.

Secondary Outcome Measures

Outcome Measure
Time Frame
Survival rate
Time Frame: The observation period is designated as 10 years from the commencement of treatment.
The observation period is designated as 10 years from the commencement of treatment.
Drug adverse events
Time Frame: The observation period is designated as 10 years from the commencement of treatment.
The observation period is designated as 10 years from the commencement of treatment.
Bone metabolism markers (BAP, NTx)
Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
BMD (DXA method): Lumbar vertebrae, femoral neck
Time Frame: Pretreatment, and post-treatment at 12 months and 24 months.
Pretreatment, and post-treatment at 12 months and 24 months.
Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG)
Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
Compliance
Time Frame: Compliance status will be entered into the database in the data center every time the study doctor prescribes drugs to the patient (1 to 3 months).
Compliance status will be entered into the database in the data center every time the study doctor prescribes drugs to the patient (1 to 3 months).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Japan Breast Cancer Research Network

Investigators

  • Principal Investigator: Satoru Iwase, MD, Department of Palliative Medicine, The University of Tokyo Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Anticipated)

May 1, 2017

Study Completion (Anticipated)

May 1, 2020

Study Registration Dates

First Submitted

February 18, 2007

First Submitted That Met QC Criteria

February 20, 2007

First Posted (Estimate)

February 21, 2007

Study Record Updates

Last Update Posted (Estimate)

March 30, 2012

Last Update Submitted That Met QC Criteria

March 28, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JBCRN-06
  • UMIN000000610

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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