Breast NeoplasmsPhase 2NCT00437359
Antiestrogen vs Aromatase Inhibitor After Adjuvant Chemotherapy for Breast Cancer
A Phase 2 study testing Toremifene citrate and Anastrozole in people with Breast Neoplasms, run by Japan Breast Cancer Research Network at 7 sites in Japan.
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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Toremifene citrate and Anastrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 7 sitesJapan
- Study dates
- May 2007to May 2020
- Phase
- Phase 2
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Japan7 sites
Kyushu Central Hospital
Fukuoka, 815-8588
Kansai Medical University Hirakata Hospital
Hirakata, 573-1191
Hirosaki University Hospital
Hirosaki, 036-8563
Hiroshima University Hospital
Hiroshima, 734-8551
Shinyahashiradai Hospital
Matsudo, 270-2253
The University of Tokyo Hospital
Tokyo, 113-8655
Nagumo Clinic
Tokyo, 141-0032
About this study
Official title: 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.
Read the 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.
- Conditions
- Breast Neoplasms
- Being tested
- Toremifene citrate, Anastrozole
- Keywords
- Breast Neoplasms, Drug Therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Toremifene citrateDrug
Also called Fareston
Toremifene citrate: 40-mg tablets by mouth once daily.
AnastrozoleDrug
Also called Arimidex
Anastrozole: 1-mg tablets by mouth once daily.
| Study group | Role | What they receive |
|---|---|---|
| Fareston | Other | Toremifene citrate: 40-mg tablets by mouth once daily. Receives: Drug: Toremifene citrate |
| Arimidex | Other | Anastrozole: 1-mg tablets by mouth once daily. Receives: Drug: Anastrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free rate
Measured: The observation period is designated as 10 years from the commencement of treatment.
Secondary outcomes (6)
Survival rate
Measured: The observation period is designated as 10 years from the commencement of treatment.
Drug adverse events
Measured: The observation period is designated as 10 years from the commencement of treatment.
Bone metabolism markers (BAP, NTx)
Measured: Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
BMD (DXA method): Lumbar vertebrae, femoral neck
Measured: Pretreatment, and post-treatment at 12 months and 24 months.
Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG)
Measured: Pretreatment, and post-treatment at 3, 6, 12, and 24 months.
Compliance
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2007 (estimated)
- Study startMay 2007
- Primary completionMay 2017 (estimated)
- Study completionMay 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Japan Breast Cancer Research Network
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Satoru Iwase, MD, Principal investigator, Department of Palliative Medicine, The University of Tokyo Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00437359
- Sponsor's protocol ID
- JBCRN-06
- Other IDs
- UMIN000000610
- Status last verified
- Mar 2012
- First submitted
- 18 Feb 2007
- Last updated
- 30 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiestrogen vs Aromatase Inhibitor After Chemotherapy for Adjuvant Setting: Efficacy of Endocrine Therapy After Chemotherapy in Postoperative Adjuvant Therapy for Breast Cancer
- ClinicalTrials.gov ID
- NCT00437359
- Acronym / sponsor ID
- JBCRN-06
- Conditions
- Breast Neoplasms
- Keywords
- Breast Neoplasms, Drug Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Japan Breast Cancer Research NetworkUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- May 2017 (estimated)
- Study completion
- May 2020 (estimated)
- First posted
- 21 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fareston | Other | Drug: Toremifene citrateToremifene citrate: 40-mg tablets by mouth once daily. |
| Arimidex | Other | Drug: AnastrozoleAnastrozole: 1-mg tablets by mouth once daily. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- Pregnant or breast feeding.
- Bilateral or inflammatory breast cancer.
- Multiple cancers.
- Life-threatening metastases.
- History of serious hypersensitivity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Toremifene citrateAlso: FarestonToremifene citrate: 40-mg tablets by mouth once daily. | Drug | Fareston |
| AnastrozoleAlso: ArimidexAnastrozole: 1-mg tablets by mouth once daily. | Drug | Arimidex |
Primary outcome
Recurrence-free rate
Time frame: The observation period is designated as 10 years from the commencement of treatment.
6 secondary outcomes
Survival rate
Time frame: 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.
Bone metabolism markers (BAP, NTx)
Time frame: 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.
Laboratory values of lipid metabolism (TC, LDL, HDL, Lp(a), TG)
Time frame: 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).
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2012.
Related trials for Breast Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Satoru Iwase, MD principal investigator
Department of Palliative Medicine, The University of Tokyo Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toremifene citrate and Anastrozole in people with Breast Neoplasms, run by Japan Breast Cancer Research Network at 7 sites in Japan.
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 8 inclusion and 6 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 30 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Japan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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. 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?
Recurrence-free rate (time frame: The observation period is designated as 10 years from the commencement of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2012.