Evaluating the Role of the Addition of Ovarian Function Suppression (OFS) to Tamoxifen in Young Women

Phase 3

• Conditions: Breast Cancer
• Interventions: Drug: goserelin; Drug: tamoxifen

• Registration Number: NCT00912548
• Lead Sponsor: Korean Breast Cancer Study Group

Brief Summary

The purpose of this study is to compare 5-year disease free survival rate (DFS rate) between the hormone receptor positive breast cancer patients who were added Goserelin to Tamoxifen for ovarian function suppression after neo-/adjuvant cytotoxic chemotherapy and the hormone receptor positive breast cancer patients who were treated with Tamoxifen.

Detailed Description

* To compare overall Survival(OS) between the patients added Goserelin(ZOLADEXTM) to Tamoxifen and the patients treated with Tamoxifen alone in premenopausal status

* To compare 5-year disease free survival rate (DFS rate) between the patients who took tamoxifen only in postmenopause and the patients added Goserelin(ZOLADEXTM) to Tamoxifen for inducing ovarian function suppression in premenopause

* To determine the tolerability and safety of Tamoxifen with or without concomitant Zoladex

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-05-31
• Status Verified: 2009-06
• Study First Submitted QC: 2009-06-02
• Study First Posted: 2009-06-03
• Last Update Submitted: 2009-06-15
• Last Update Posted: 2009-06-16
• Primary Completion: 2015-12
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 1234

Inclusion Criteria

1. Patients must have undergone excision of the primary breast mass, proven histologically to be invasive breast adenocarcinoma.
2. Patients must be within 3 months after the last cycle of chemotherapy.
3. Patients must have the history of normal menstruation prior to the start of chemotherapy.
4. Stage I, II or III
5. Woman, less than or equal to 45 years of age
6. Hormone receptor status : ER+ve and/or PgR+ve
7. WHO performance status 0, 1 or 2.
8. Patients who were treated with cytotoxic chemotherapy in pre- or post- surgery.
9. Adequate haematological function defined by haemoglobin 10g/dL, neutrophil count 1.5x109/L and platelets 100x109/L.
10. Adequate hepatic function defined by AST and ALT 2.5xupper limit of normal. Alkaline phosphatase 5xupper limit of normal, unless bone metastases in the absence of liver disease. Renal function adequate defined by creatinine<175mmol/L.

Exclusion Criteria

1. Patients whose primary breast cancer was classified as:

   • ER(-),ER unknown

2. Patients with the history of hysterectomy or oophorectomy

3. Sarcomas or squamous cell carcinomas of the breast are not eligible.

4. Patients with malignancies (other than breast cancer) within the last 5 years, except for adequately treated in situ carcinoma of the cervix or basal cell / squamous cell carcinoma of the skin.

5. Investigational drugs given within the previous 4 weeks.

6. Patients known to be on any unlicensed non-cancer investigational agent.

7. Patients with thrombocytopaenia (platelets <100 x 109/l or on anti- coagulant therapy (contra-indicated due to risk of bleeding with i.m. injection of Zoladex).

8. Patients treated with CMF(cyclophosphamide/methotrexate/5-fluorouracil) as prior chemotherapy

9. Patients who are pregnant or lactating are ineligible.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
TAM+OFS(E) group	goserelin	Patients should be premenopausal women ,prior to the start of chemotherapy, less than or equal to 45 years of age with oestrogen receptor positive ± progesterone receptor positive who have undergone a primary mass excision, received an neo-/adjuvant chemotherapy ± radiotherapy for their stage I, II or III breast cancer. This arm is ovarian suppression group which have a various starting time of ovarian function suppression after neo-/adjuvant chemotherapy. Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. After that, the patients will complete taking tamoxifen 20mg/day for 5 years.
TAM(D) group	tamoxifen	Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 0, 6, 12, 18 and 24 months since the baseline asTsessment(0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized into the additional ovarian function suppression group or tamoxifen only group. The latter will complete taking tamoxifen 20mg/day for 5 years.
TAM+OFS(E) group	tamoxifen	Patients should be premenopausal women ,prior to the start of chemotherapy, less than or equal to 45 years of age with oestrogen receptor positive ± progesterone receptor positive who have undergone a primary mass excision, received an neo-/adjuvant chemotherapy ± radiotherapy for their stage I, II or III breast cancer. This arm is ovarian suppression group which have a various starting time of ovarian function suppression after neo-/adjuvant chemotherapy. Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. After that, the patients will complete taking tamoxifen 20mg/day for 5 years.
TAM(B)	tamoxifen	Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 6, 12, 18 and 24 months since the baseline assessment (0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized into the additional ovarian function suppression group or tamoxifen only group. This group, patients are premenopausal women, they will be randomized into tamoxifen only group, complete taking tamoxifen 20mg/day for 5 years.
TAM+OFS (C)	goserelin	Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 6, 12, 18 and 24 months since the baseline assessment (0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized. This group, patients are premenopausal women, they will be randomized into the additional ovarian function suppression group. Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. Then, Patients will complete taking tamoxifen 20mg/day for 5 years.
TAM+OFS (C)	tamoxifen	Patients, less than or equal to 45 years of age with hormone receptor positive breast cancer will be enrolled. Included All the patients have already treated by surgery, neo- or adjuvant chemotherapy ±and/or radiotherapy before enrolment. At 6, 12, 18 and 24 months since the baseline assessment (0), the ovarian function status will be evaluated by menstruation status or serum FSH level. If the patients are regarded as the premenopausal women, they will be randomized. This group, patients are premenopausal women, they will be randomized into the additional ovarian function suppression group. Ovarian function suppression will be done by administration of LHRH agonist (ZOLADEXTM) for 2 years. Then, Patients will complete taking tamoxifen 20mg/day for 5 years.

Primary Outcome Measures

Name	Time	Method
all cause recurrence	the first 5 years after surgery

Trial Locations

Locations (1)

Department of Surgery, Korea Cancer Center Hospital; 🇰🇷 Seoul, Korea, Republic of