Antiestrogen vs Aromatase Inhibitor After Adjuvant Chemotherapy for Breast Cancer

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00437359
• Other study ID #: JBCRN-06
• Secondary ID: UMIN000000610
• Status: Terminated
• Phase: Phase 2
• First received: February 18, 2007
• Last updated: March 28, 2012
• Start date: May 2007
• Est. completion date: May 2020

Study information

• Verified date: March 2012
• Source: Japan Breast Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 240
• Est. completion date: May 2020
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Toremifene citrate
Toremifene citrate: 40-mg tablets by mouth once daily.
• Anastrozole
Anastrozole: 1-mg tablets by mouth once daily.

Locations

Country	Name	City	State
Japan	Kyushu Central Hospital	Fukuoka
Japan	Kansai Medical University Hirakata Hospital	Hirakata
Japan	Hirosaki University Hospital	Hirosaki
Japan	Hiroshima University Hospital	Hiroshima
Japan	Shinyahashiradai Hospital	Matsudo
Japan	Nagumo Clinic	Tokyo
Japan	The University of Tokyo Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Japan Breast Cancer Research Network

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free rate		The observation period is designated as 10 years from the commencement of treatment.	No
Secondary	Survival rate		The observation period is designated as 10 years from the commencement of treatment.	No
Secondary	Drug adverse events		The observation period is designated as 10 years from the commencement of treatment.	Yes
Secondary	Bone metabolism markers (BAP, NTx)		Pretreatment, and post-treatment at 3, 6, 12, and 24 months.	No
Secondary	BMD (DXA method): Lumbar vertebrae, femoral neck		Pretreatment, and post-treatment at 12 months and 24 months.	No
Secondary	Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG)		Pretreatment, and post-treatment at 3, 6, 12, and 24 months.	No
Secondary	Compliance		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).	No