Oestrogen receptor (ER) positive advanced breast cancer (ABC) in pre-menopausal women
Conditions
Interventions
Trade Name: Zoladex LA 10.8 mg implant
Pharmaceutical Form: Implant
INN or Proposed INN: Goserelin
Other descriptive name: (as Goserelin acetate)
Concentration unit: mg milligram(s)
Concentration type
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Provision of written informed consent - For the PK analyses in this study (see Section 4.5), optional additional blood samples will be taken from those patients who provide written informed consent to confirm that they are willing to participate in this part of the study. This consent will be in addition to their written informed consent to confirm their willingness to participate in the main study. See Section 8.3.1 for further information 2. Female =18 years and pre-menopausal - Pre-menopausal defined as 1) last menses within 1 year of administration of study drug, and 2) E2 =10 pg/mL and FSH =30 mIU/mL within 4 weeks of administration of study drug. For patients who have had a hysterectomy, it is acceptable to meet only criterion 2. 3. Histological/cytological confirmation of locally advanced or metastatic breast cancer and are candidates to receive hormonal therapy as therapy for advanced disease. Patients may have received prior adjuvant chemotherapy, radiotherapy or hormonal therapy for EBC 4. Documented evidence of hormone sensitivity (ER positive) of primary or secondary tumour tissue 5. World Health Organization (WHO) Performance status of 0, 1 or 2 (see Appendix D) 6. At least one measurable lesion (not located in a previously irradiated area) according to RECIST with the exception of patients with bone metastases only or complete remission after prior taxane- or anthracycline based first line chemotherapy for ABC (stage IV). See Section 3.3.3, exclusion criterion 4, for further details of eligibility criteria concerning prior first line chemotherapy for ABC. Patients with bone metastases only must fulfil one of the following conditions: - Have osteolytic lesions identifiable by bone x-ray (patients with productive bone lesions only, as identified by bone x-ray, are not eligible), - Have bone lesions identified by MRI or computed tomography scan (patients with productive bone lesions only, as identified by MRI or computed tomography scan, are eligible). Patients with complete remission after prior taxane- or anthracycline based first line chemotherapy for ABC must fulfil one of the following conditions: - Have had at least one measurable lesion (not located in a previously irradiated area) according to RECIST prior to taxane- or anthracycline based first line chemotherapy for ABC, - Have had bone metastases meeting the criteria listed above prior to taxane- or anthracycline based first line chemotherapy for ABC. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients who have received tamoxifen or other hormonal therapies as adjuvant therapy for EBC in the 24 weeks before administration of study drug; prior treatment with hormonal therapies for ABC 2. Patients who have received LHRHa as adjuvant therapy for EBC in the 48 weeks before administration of study drug (up to 2 years of adjuvant treatment with an LHRHa is permitted) 3. Patients who have received any radiotherapy for EBC or ABC within 4 weeks before administration of study drug 4. Prior first line chemotherapy for ABC with the exception of taxane- or anthracycline-based chemotherapy providing that a) there is no evidence of progressive disease since the start of the chemotherapy and b) the patient has pre-menopausal status after starting chemotherapy. Patients who have had prior chemotherapy for ABC must have had at least one menstrual period since starting chemotherapy. Any taxane- or anthracycline-based chemotherapy must be completed at least 4 weeks prior to Day 1 of this study. (Prior adjuvant chemotherapy for EBC is allowed except when it has been administered within 4 weeks before study drug administration ) 5. Prior treatment with herceptin for EBC within 4 weeks before study drug administration; prior treatment with herceptin for ABC 6. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic involvement, or any degree (proven or suspected) of brain or leptomeningeal involvement (past or present) or symptomatic pulmonary lymhangitic spread. Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not compromised as a result of disease 7. Estimated survival less than 24 weeks from the start of study therapy (Day 1) based on clinical judgment 8. History (within previous 3 years before administration of study drug) of systemic malignancy other than breast cancer with the exception of basal cell/squamous cell carcinoma of the skin or cancer of the cervix that has been satisfactorily controlled 9. Platelets 1.5x upper limit of reference range (ULRR); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5xULRR if no demonstrable liver metastases or >5xULRR in presence of liver metastases 10. Any other significantly abnormal laboratory test result at baseline that would place the patient at unusual risk or confound the results of the study as assessed by the treating investigator 11. Treatment with a non-approved or experimental drug within the preceding 12 weeks before administration of study drug 12. Patients with a relevant history of any severe concomitant disease that would place the patient at unusual risk or confound the results of the study (eg, a strong family history of osteoporosis or severe renal or hepatic impairment) as assessed by the treating investigator 13. Patients who, for whatever reason (eg, confusion, infirmity, alcoholism) are unlikely to comply with study requirements as assessed by the treating investigator 14. Patients considered by the investigator to be at risk of transmitting any infection through blood or other body fluids including the agents for acquired immune deficiency syndrome or other sexually transmitted disease or hepatitis 15. History of bleeding diathesis (ie, disseminated intravascular coagulation or clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet therapy and low dose warfarin) 16. History of any hypersensitivity to act
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate whether ZOLADEX 10.8 mg is non-inferior to ZOLADEX 3.6 mg in pre-menopausal women with oestrogen receptor (ER) positive advanced breast cancer (ABC) by assessment of progression-free survival (PFS) at 24 weeks.;Primary end point(s): The primary study variable measurement is disease progression. The primary outcome variable is the Progression Free Survival; this is used as the basis for the sample size calculations;Secondary Objective: • To provide supportive data confirming that ZOLADEX 10.8 mg every 12 weeks is non-inferior to ZOLADEX 3.6 mg every 4 weeks by assessment of: - Objective response rate (ORR) at 24 weeks, with response defined as complete or partial response as determined by Response Evaluation Criteria In Solid Tumours (RECIST) criteria - Oestradiol (E2) serum concentrations at 24 weeks • To compare the safety and tolerability profile of ZOLADEX 10.8 mg and ZOLADEX 3.6 mg by assessment of adverse events (AEs) • To assess goserelin PK in Japanese and Caucasian patients who have received ZOLADEX 10.8 mg by assessment of goserelin plasma concentration-time profiles. | — |
Countries
Czech Republic, Italy
Outcome results
None listed