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

Korean Breast Cancer Study Group

Status and phase: Unknown; Phase 3

Conditions: Breast Cancer

Treatments: Drug: tamoxifen; Drug: goserelin

Study type: Interventional

Funder types: Other

Identifiers

NCT00912548

KBCSG005

Details and patient eligibility

About

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.

Full 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

Enrollment: 1,234 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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1,234 participants in 5 patient groups

TAM+OFS(E) group

Experimental group

Description:

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.

Treatment:

Drug: goserelin

Drug: tamoxifen

TAM(D) group

Active Comparator group

Description:

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.

Treatment:

Drug: tamoxifen

Permanent postmenopausal(A) group

No Intervention group

Description:

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. Eligible patients except for premenopausal status at the baseline will be followed up until 2 years after the baseline assessment for evaluating the menopausal status. This group still remains to postmenopausal status and will taking tamoxifen 20mg/day for 5 years if they remain in the study.

TAM(B)

Active Comparator group

Description:

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.

Treatment:

Drug: tamoxifen

TAM+OFS (C)

Experimental group

Description:

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.

Treatment:

Drug: goserelin

Drug: tamoxifen