Health Condition 1: null- Locally Advanced or Metastatic Breast Cancer
Conditions
Interventions
Intervention1: Everolimus (RAD001)and exemestane: All patients will receive everolimus 10 mg per day and exemestane 25 mg per day once daily by oral route.
Patients will continue to be treated per pro
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Adult women (greater than or equal to 18 years of age) with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. 2. Histological or cytological confirmation of estrogen receptor positive (ER positive) breast cancer. 3. Postmenopausal women. Ovarian radiation or treatment with a luteinizing hormonereleasing hormone (LHRH) agonist (goserelin acetate or leuprolide acetate) does not satisfy this inclusion criterion. Postmenopausal status is defined by one of the following: ? Age greater than or equal to 55 years and one year or more of amenorrhea ? Age greater than 55 years and one year or more of amenorrhea, with estradiol assay less than 20 pg per ml and/or post-menopausal levels of FSH and LH per local institutional standards ? Prior hysterectomy, with estradiol assay less than 20 pg per ml and/or post-menopausal levels of FSH and LH per local institutional standards ? Surgical menopause with bilateral oophorectomy. 4. Disease refractory to non-steroidal aromatase inhibitors (NSAI), defined as: ? Recurrence while on, or within 12 months (365 days) of completion of adjuvant therapy with letrozole or anastrozole, or ? Progression while on, or within one month (30 days) of completion of letrozole or anastrozole treatment for ABC. ? Notes: Letrozole or anastrozole do not have to be the last treatment prior to study baseline. Patients may have received one prior chemotherapy line for ABC, or have received other endocrine treatments such as tamoxifen, or fulvestrant. 5. Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment. ? Notes: The last line of therapy may be any other treatment than exemestane and mTOR inhibitors. Patients must have recovered to grade 1 or better from any adverse events related to previous therapy (except alopecia) prior to enrolment. 6. Patients must have: ? Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension greater than or equal to 20 mm with conventional imaging techniques or greater than or equal to 10 mm with spiral CT or MRI, or ? Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above. Note: Lymph nodes must be greater than or equal to 15 mm in the short axis to be considered measurable Patients with bone lesions and at least one measurable lesion are considered as having measurable disease If bone lesions have been previously irradiated, at least one lesion must have clearly progressed since the radiotherapy by CT, MRI or X-ray for trial entry (in the absence of measurable disease). 7. Adequate bone marrow and coagulation function as shown by: ? Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10 raised to 9 per L ? Platelets greater than or equal to 100 ? 10 raised to 9 per L ? Hemoglobin (Hgb) greater than or equal to 9.0 g per dL ? INR less than or equal to 2. 8. Adequate liver function as shown by: ? Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 ULN (or less than or equal to 5 if hepatic metastases a
Exclusion criteria
Exclusion criteria: 1. Patients overexpressing HER2 by local laboratory testing (IHC 3 positive staining or in situ hybridization positive), based on the most recent test. Patients with IHC 2 positive must have a negative in situ hybridization test. 2. Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites). 3. Patients with more than one prior chemotherapy line for treating metastatic breast cancer. A chemotherapy line is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent, given for a minimum of 21 days. A cytotoxic chemotherapy regimen that lasted less than 21 days and was discontinued for a reason other than disease progression is not accounted as a prior line of chemotherapy. 4. Previous treatment with exemestane or mTOR inhibitors. 5. Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin). 6. Any other malignancy within 5 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous skin cell carcinoma, or non-melanoma skin cancer. 7. Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment. 8. Patient receiving hormone replacement therapy (HRT). Patient may be enrolled after discontinuation of HRT. 9. History of brain or other CNS metastases. 10. Treatment with immunosuppressive agents or chronic corticosteroids, with the following exceptions: ? Patients on stable low dose of systemic corticosteroids for at least two weeks before enrolment ? Corticosteroids used in topical applications (e.g. cream), inhaled sprays, eye drops or local (e.g. intra-articular) injections. 11. Bilateral diffuse lymphangitic carcinomatosis. 12. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required. 13. Active, bleeding diathesis. Patients treated with anti-vitamin K medication, LMWH, or anti-platelet medication must have an INR = 2.0. 14. Any severe and / or uncontrolled medical conditions such as: a. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction less than or equal to 6 months prior to enrolment, serious uncontrolled cardiac arrhythmia b. Uncontrolled diabetes as defined by fasting serum glucose more than 1.5 times ULN c. Acute and chronic, active infectious disorders (except for Hep B and Hep C positive patients) and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy d. Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome) e. Active skin, mucosa, ocular or gastro-intestinal disorders of Grade greater than 1 f. Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability profile of everolimus in post-menopausal women with ER positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitor therapy in Novartis Oncology EGM countries.Timepoint: safety and tolerability will be based mainly on the frequency of adverse events, including the laboratory values that qualify as adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| To provide early access & To evaluate the efficacy of everolimus in postmenopausal women with ER positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a nonsteroidal aromatase inhibitor therapy in EGM countries. -To assess changes from baseline in Eastern Cooperative Oncology Group (ECOG) performance status over the study period.Timepoint: Efficacy endpoints will be analyzed on the Full Analysis Set (primary analysis) and on the Per Protocol Set (supportive analysis). | — |
Countries
Algeria, Australia, Egypt, India, Indonesia, Jordan, Malaysia, Morocco, Oman, Republic of Korea, South Africa, Taiwan, Thailand, Tunisia, Turkey, Viet Nam
Contacts
Public ContactDr Manish Mistry
Novartis India Ltd.
Outcome results
None listed