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

Sponsor

Korean Breast Cancer Study Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT00912548

Collaborator

(none)

1,234

Enrollment

Location

Arms

Duration (Months)

15.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: goserelin Drug: tamoxifen	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1234 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised Phase III Study for Evaluating the Role of the Addition of Ovarian Function Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain in Premenopause or Regain Menstruation After Chemotherapy

Study Start Date :

May 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAM+OFS(E) group 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.	Drug: goserelin Zoladex™ administration: Zoladex™ depot is available as a sterile disposable syringe. The depot is administered subcutaneously under the abdominal skin under sterile conditions. If necessary the injection site may be pre-treated with a local anaesthetic. Sequence of administration Zoladex depot: The substance is administered for 24 months (2 years) at 28-day intervals (a period of 34 days between 2 administrations must not be exceeded). Dosage: Each depot contains 3.6mg Zoladex. The substance Zoladex is contained in a while cylindrical rodlet . Storage instructions for Zoladex™ Zoladex™ is kept a room temperature. Other Names: Zoladex® Drug: tamoxifen Dose and period of Tamoxifen therapy: Tamoxifen is administered in tablet form. Each day 2 X 10 mg or 1 X 20 mg Tamoxifen are taken in the form of the respective tablet. Storage instructions for Tamoxifen Tamoxifen is stored at room temperature away from light. Other Names: Nolvadex
Active Comparator: TAM(D) group 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.	Drug: tamoxifen Dose and period of Tamoxifen therapy: Tamoxifen is administered in tablet form. Each day 2 X 10 mg or 1 X 20 mg Tamoxifen are taken in the form of the respective tablet. Storage instructions for Tamoxifen Tamoxifen is stored at room temperature away from light. Other Names: Nolvadex
No Intervention: Permanent postmenopausal(A) group 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.
Active Comparator: TAM(B) 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.	Drug: tamoxifen Dose and period of Tamoxifen therapy: Tamoxifen is administered in tablet form. Each day 2 X 10 mg or 1 X 20 mg Tamoxifen are taken in the form of the respective tablet. Storage instructions for Tamoxifen Tamoxifen is stored at room temperature away from light. Other Names: Nolvadex
Experimental: TAM+OFS (C) 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.	Drug: goserelin Zoladex™ administration: Zoladex™ depot is available as a sterile disposable syringe. The depot is administered subcutaneously under the abdominal skin under sterile conditions. If necessary the injection site may be pre-treated with a local anaesthetic. Sequence of administration Zoladex depot: The substance is administered for 24 months (2 years) at 28-day intervals (a period of 34 days between 2 administrations must not be exceeded). Dosage: Each depot contains 3.6mg Zoladex. The substance Zoladex is contained in a while cylindrical rodlet . Storage instructions for Zoladex™ Zoladex™ is kept a room temperature. Other Names: Zoladex® Drug: tamoxifen Dose and period of Tamoxifen therapy: Tamoxifen is administered in tablet form. Each day 2 X 10 mg or 1 X 20 mg Tamoxifen are taken in the form of the respective tablet. Storage instructions for Tamoxifen Tamoxifen is stored at room temperature away from light. Other Names: Nolvadex

Outcome Measures

Primary Outcome Measures

all cause recurrence [the first 5 years after surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have undergone excision of the primary breast mass, proven histologically to be invasive breast adenocarcinoma.
Patients must be within 3 months after the last cycle of chemotherapy.
Patients must have the history of normal menstruation prior to the start of chemotherapy.
Stage I, II or III
Woman, less than or equal to 45 years of age
Hormone receptor status : ER+ve and/or PgR+ve
WHO performance status 0, 1 or 2.
Patients who were treated with cytotoxic chemotherapy in pre- or post- surgery.
Adequate haematological function defined by haemoglobin 10g/dL, neutrophil count 1.5x109/L and platelets 100x109/L.
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:

Patients whose primary breast cancer was classified as:

ER(-),ER unknown

Patients with the history of hysterectomy or oophorectomy
Sarcomas or squamous cell carcinomas of the breast are not eligible.
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.
Investigational drugs given within the previous 4 weeks.
Patients known to be on any unlicensed non-cancer investigational agent.
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).
Patients treated with CMF(cyclophosphamide/methotrexate/5-fluorouracil) as prior chemotherapy
Patients who are pregnant or lactating are ineligible.