Antiestrogen vs Aromatase Inhibitor After Adjuvant Chemotherapy for Breast Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Japan Breast Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00437359
First received: February 18, 2007
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Breast Neoplasms
Drug: Toremifene citrate
Drug: Anastrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antiestrogen vs Aromatase Inhibitor After Chemotherapy for Adjuvant Setting: Efficacy of Endocrine Therapy After Chemotherapy in Postoperative Adjuvant Therapy for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Japan Breast Cancer Research Network:

Primary Outcome Measures:
  • Recurrence-free rate [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival rate [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: No ]
  • Drug adverse events [ Time Frame: The observation period is designated as 10 years from the commencement of treatment. ] [ Designated as safety issue: Yes ]
  • Bone metabolism markers (BAP, NTx) [ Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months. ] [ Designated as safety issue: No ]
  • BMD (DXA method): Lumbar vertebrae, femoral neck [ Time Frame: Pretreatment, and post-treatment at 12 months and 24 months. ] [ Designated as safety issue: No ]
  • Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG) [ Time Frame: Pretreatment, and post-treatment at 3, 6, 12, and 24 months. ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: May 2007
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Fareston
Toremifene citrate: 40-mg tablets by mouth once daily.
Drug: Toremifene citrate
Toremifene citrate: 40-mg tablets by mouth once daily.
Other Name: Fareston
Arimidex
Anastrozole: 1-mg tablets by mouth once daily.
Drug: Anastrozole
Anastrozole: 1-mg tablets by mouth once daily.
Other Name: Arimidex

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00437359

Locations
Japan
Kyushu Central Hospital
Fukuoka, Japan, 815-8588
Kansai Medical University Hirakata Hospital
Hirakata, Japan, 573-1191
Hirosaki University Hospital
Hirosaki, Japan, 036-8563
Hiroshima University Hospital
Hiroshima, Japan, 734-8551
Shinyahashiradai Hospital
Matsudo, Japan, 270-2253
Nagumo Clinic
Tokyo, Japan, 141-0032
The University of Tokyo Hospital
Tokyo, Japan, 113-8655
Sponsors and Collaborators
Japan Breast Cancer Research Network
Investigators
Principal Investigator: Satoru Iwase, MD Department of Palliative Medicine, The University of Tokyo Hospital
  More Information

No publications provided

Responsible Party: Japan Breast Cancer Research Network
ClinicalTrials.gov Identifier: NCT00437359     History of Changes
Other Study ID Numbers: JBCRN-06, UMIN000000610
Study First Received: February 18, 2007
Last Updated: March 28, 2012
Health Authority: Japan: Institutional Review Board

Keywords provided by Japan Breast Cancer Research Network:
Breast Neoplasms
Drug Therapy

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Anastrozole
Toremifene
Aromatase Inhibitors
Estrogen Receptor Modulators
Estrogen Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Selective Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 16, 2014