Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Tamoxifen

Hormones

Everolimus

Fulvestrant

Exemestane

Letrozole

Estrogens

Estrogen Receptor Modulators

Anastrozole

Estrogen Antagonists

Estrogen Receptor Antagonists

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Aromatase Inhibitors

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Everolimus will be administered at a dose of 10 mg PO daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses.

Toremifine

Denise A. Yardley, MD

Many patients with ER-positive or PR-positive breast cancer are treated with endocrine therapy. Although most ER/PR-positive tumors initially respond to hormonal therapy, patients often experience disease progression. Everolimus, in combination with exemestane, has shown activity in endocrine-resistant disease. This study will evaluate the efficacy of Everolimus+ anti-estrogen therapy in patients with ER-positive metastatic breast cancer who have progressed after receiving anti-estrogen therapy.

This is a multi-centered, open-labeled, Phase II study on metastastic breast cancer (MBC). The patient population includes locally recurrent or MBC patients with cytologically or histologically confirmed hormone receptor-positive breast cancer who have demonstrated disease progression on prior anti-estrogen therapy or therapies. Investigators propose to evaluate the efficacy of Everolimus in patients with ER-positive (estrogen receptor-positive) metastatic breast cancer who have progressed on anti-estrogen therapy. Forty-six (46) patients are planned for enrollment in the trial.

Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer

Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer

PFS is defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, or death on study. Participants who are alive and free from disease progression will be censored at the date of last radiologic tumor assessment. Participants who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. Participants who do not have a post-baseline tumor assessment will be censored at the date of first treatment (Day 1).

Assessments were made through analysis of the reported incidence of treatment-emergent AEs. All participants who received at least one dose of protocol treatment were followed for safety. Adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST version 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.

The proportion of patients with Complete Response (CR) or Partial Response (PR) or 6 months or more of Stable Disease (SD). A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters. SD is not meeting the criteria for PR or a 20% increase in target lesions called Progressive Disease (PD).

Only those patients who achieved Complete Response or Partial Response will be included in the summaries of DOR. DOR is defined as time from first date of response of CR or PR to disease progression or death as defined by RECIST v1.1 criteria. Participants who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.

Defined as the time from date of first study treatment to date of death due to any cause. Patients who are alive will be censored at the date of last known date alive.

Novartis

SCRI Development Innovations, LLC

All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Everolimus will be administered at a dose of 10 mg PO daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses.

Everolimus

Exemestane: Anti-estrogen therapy

Tamoxifen: Anti-estrogen therapy

Fulvestrant: Anti-estrogen therapy

Anastrozole: Anti-estrogen therapy

Letrozole: Anti-estrogen therapy

Toremifine: Anti-estrogen therapy

Everolimus will be administered at a dose of 10 mg by mouth daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses. A treatment cycle was defined as 4 weeks, with radiological evaluations every 8 weeks.

Everolimus

Exemestane: Anti-estrogen therapy

Tamoxifen: Anti-estrogen therapy

Fulvestrant: Anti-estrogen therapy

Anastrozole: Anti-estrogen therapy

Letrozole: Anti-estrogen therapy

Toremifine: Anti-estrogen therapy

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

All patients who received at least one dose of treatment.

Senior Director, Regulatory Science

Participants who received at least 1 cycle of study treatment and had at least one post-baseline radiologic assessment were evaluable for PFS analysis per protocol. 36 of the total 48 patients were analyzed for PFS. The remaining 12 treated patients did not meet this criteria to be analyzed.

Median Progression Free Survival (PFS)

Number of participants who received at least one dose of study drug.

Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability

Participants who received at least 1 cycle of study treatment and had at least one post-baseline radiologic assessment. 36 of the total 48 patients were analyzed for PFS. The remaining 12 treated patients did not meet this criteria to be analyzed.

Number of Patients With an Objective Response (CR or PR) Also Called the Overall Response Rate (ORR).

Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR)

Only those patients who achieved Complete Response or Partial Response will be included in the summaries of DOR. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.

Median Time From First Occurrence of CR or PR to Disease Progression or Death Also Called Duration of Response (DOR)

Participants who received at least 1 cycle of study treatment and had at least one post-baseline radiologic assessment were evaluable for OS analysis per protocol. 36 of the total 48 patients were analyzed for OS. The remaining 12 treated patients did not meet this criteria to be analyzed.

Spots Global Cancer Trial Database for Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer

Trial Identification

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Study Description

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