Advanced or metastatic hormone receptor positive breast cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up •Procedures conducted as a part of routine clinical management of the subject and obtained prior to signed informed consent may be utilized for Screening or Baseline purposes provided these tests are obtained as specified in the protocol. 2. Subjects must have measurable disease OR must be evaluable for disease progression, as defined in the protocol. 3.Age = 18 years. 4.Postmenopausal women as defined in the protocol. 5.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. 6.Histologically or cytologically confirmed estrogen receptor (ER) and/or progesterone receptor (PgR) positive carcinoma of the breast with unresectable, locally advanced and/or metastatic (AJCC Stage IV) disease. 7.Subjects must have received prior hormonal therapy for the treatment of breast cancer as defined in the protocol 8.Subjects may have received up to 1 week of exemestane for metastatic disease prior to randomization. 9.Subjects whose tumors overexpress ErbB2 are eligible provided that they have progressed following therapy that included trastuzumab and/or lapatinib. 10.Adequate hematologic, hepatic, and renal function as defined in Table 1 in the protocol. 11.Subjects must have discontinued hormone replacement therapy (HRT) at least 28 days prior to receiving the first dose of randomized therapy. 12.Radiotherapy prior to initiation of randomized therapy is allowed to a limited area if it is not the sole site of disease. Subjects must have completed treatment at least 2 weeks prior to starting study drugs, and must have recovered from all treatment-related toxicities. 13. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, is not permitted; 14. Ability to swallow and retain oral medication. 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) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Prior use of pazopanib or exemestane (except as noted in inclusion criteria # 8). 2.Subjects who are pre-menopausal. 3.Known central nervous system (CNS) metastases or leptomeningeal carcinomatosis. 4.History of another malignancy. 5.Clinically significant gastrointestinal abnormalities which might interfere with oral dosing. 6. Presence of uncontrolled infection. 7. Prolongation of corrected QT interval (QTc) = 480msecs. 8. History of any one or more of cardiovascular conditions as defined in the protocol 9. Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). 10. Has had any chemotherapy or biological anti-cancer therapy within the last 28 days and/or has not recovered from any prior therapy (except stated in inclusion criteria # 9). 11. Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug. 12. Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors. 13. Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity. 14. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =150mmHg or diastolic blood pressure (DBP) of = 90mmHg], as described in the protocol. 15. History of cerebrovascular accident (CVA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months, as described in the protocol. 16. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. 17. Evidence of active bleeding or bleeding diathesis. 18. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures 19. Is unable or unwilling to discontinue predefined prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare progression free survival (PFS) of treatment with exemestane and pazopanib versus exemestane plus placebo in postmenopausal subjects with hormone receptor positive (ER+ and/or PgR+) unresectable, locally advanced or metastatic breast cancer subjects who have progressed on prior hormonal treatment.;Secondary Objective: The secondary objectives of the study are to compare exemestane plus pazopanib with exemestane plus placebo with respect to: •Safety and tolerability •Overall response rate in subjects with measurable disease •Overall survival •Change in health-related quality of life relative to baseline Translational Research Objectives •Determine the relationship of intra-tumoral expression (in metastatic site) of ER, PgR, HER2 and downstream markers to the response of exemestane alone or in combination with pazopanib •Determine if breast cancer subtypes can predict for better response to exemestane alone or in combination with pazopanib •Determine the relationship between changes in [serum/plasma] protein profile that are associated with response to exemestane alone or in combination with pazopanib •Investigate the relationship between genetic variants in germline (host) DNA and the efficacy, safety and tolerability of exemestane alone or in combination with pazopanib;Primary end point(s): The primary objective of the study is to compare progression free survival (PFS) of treatment with exemestane and pazopanib versus exemestane plus placebo in postmenopausal subjects with hormone receptor positive (ER+ and/or PgR+) unresectable, locally advanced or metastatic breast cancer subjects who have progressed on prior hormonal treatment. | — |
Countries
Germany
Outcome results
None listed