Safety and Efficacy Study of Sapanisertib in Combination With Exemestane or Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Metastatic Breast Cancer

Completed · Phase 2

Conditions studied: Breast Cancer

In brief

This is a phase 1b/2 study of the safety and efficacy of sapanisertib (MLN0128) in combination with exemestane or fulvestrant therapy in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus in combination with exemestane or fulvestrant.

Key facts

Study ID: NCT02049957
Run by: Calithera Biosciences, Inc
People needed: 118
Starts: 2014-02-13
Expected to finish: 2018-06-29
Last updated by the study team: 2023-02-08

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

Each patient must meet all of the following inclusion criteria to be enrolled in the study:
Phase 1b and Phase 2
Advanced or metastatic breast cancer.
Histological or cytological confirmation of ER+ status (defined as > 1% positive tumor cells), and histological or cytological confirmation of HER2-negative (HER2-) status by local laboratory testing using criteria in the American Society of Oncology (ASCO)/College of American Pathologists (CAP) Clinical Practice Guideline update.
Female patients 18 years of age or older who are postmenopausal for at least 1 year before the Screening visit, where menopause is defined by: Age ≥ 55 years and 1 year or more of amenorrhea. Surgical menopause with bilateral oophorectomy
Age < 55 years and 1 year or more of amenorrhea, with an estradiol assay < 20 pg/mL
Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.
Have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
Brain metastases which have been treated
No evidence of disease progression for ≥ 3 months or hemorrhage after treatment
Off-treatment with dexamethasone for 4 weeks before administration of the first dose of MLN0128
No ongoing requirement for dexamethasone or anti-epileptic drugs
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Clinical laboratory values as specified below within 4 weeks before the first dose of MLN0128:
Bone marrow reserve consistent with absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L; platelet count ≥ 100 x 10\^9/L; hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present)
Creatinine clearance ≥ 50 mL/min based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection
Fasting serum glucose ≤ 130 mg/dL and fasting triglycerides ≤ 300 mg/dL
Left ventricular ejection fraction (LVEF) within 5 absolute percentage points of institutional standard of normal as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before the first dose of MLN0128 (ie, if the institutional standard of normal is 50%, LVEF may be as low as 45% to be eligible for the study).
Able to provide paraffin blocks or a minimum of 10 unstained slides of available archival tumor tissues (paraffin blocks are preferred). If archival tumor tissue is not available, a tumor biopsy may be performed before the patient begins treatment with MLN0128. If fewer than 10 slides are available or the tumor content/area requirements are not met, study eligibility will be determined upon discussion with the sponsor.
Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
Voluntary written consent must be given before the performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Phase 1b Only: In addition to the previously mentioned inclusion criteria, each patient must meet the following inclusion criterion to be enrolled in the phase 1b portion of the study:
Patients may have SD or disease progression during their most recent treatment with exemestane or fulvestrant, or everolimus in combination with either exemestane (any country) or fulvestrant (US only). Exemestane or fulvestrant in combination with MLN0128 can also be initiated as a new line of therapy.
Phase 2 Only: In addition to the previously mentioned inclusion criteria, each patient must meet all of the following inclusion criteria to be enrolled in the phase 2 portion of the study:

You may not qualify if…

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
Phase 1b and Phase 2
Prior anticancer therapy or other investigational therapy within 2 weeks before administration of the first dose of MLN0128 (except for exemestane or fulvestrant, which should be continued). Treatment with everolimus must be discontinued 2 weeks before administration of the first dose of MLN0128.
Chronic concomitant therapy with bisphosphonates or denosumab for the prevention of bone metastases. Concomitant treatment with bisphosphonates or denosumab is permitted for treatment of osteoporosis or management of existing bone metastases if initiated at least 4 weeks before administration of the first dose of MLN0128.
Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either IV or oral steroids, excluding inhalers) within 1 week before administration of the first dose of MLN0128 (patients already receiving erythropoietin on a chronic basis for ≥ 4 weeks are eligible).
Previous treatment with dual PI3K/mTOR inhibitors or TORC1/2 inhibitors.
Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128.
Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 7%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met.
Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study.
Known human immunodeficiency virus infection.
History of any of the following within the last 6 months before administration of the first dose of MLN0128:
Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia)
Placement of a pacemaker for control of rhythm
New York Heart Association Class III or IV heart failure
Pulmonary embolism
Significant active cardiovascular or pulmonary disease before administration of the first dose of MLN0128, including:
Uncontrolled hypertension (ie, systolic blood pressure > 180 mm Hg; diastolic blood pressure > 95 mm Hg)
Pulmonary hypertension
Uncontrolled asthma or oxygen saturation < 90% by arterial blood gas analysis or pulse oximetry on room air
Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention; or history of valve replacement
Medically significant (symptomatic) bradycardia
History of arrhythmia requiring an implantable cardiac defibrillator
Baseline prolongation of the rate-corrected QT interval (QTc; eg, repeated demonstration of QTc interval > 480 ms, or history of congenital long QT syndrome, or torsades de pointes)

Where it is running

Los Angeles Hematology — Los Angeles, California, United States
University of California at San Francisco (PARENT) — San Francisco, California, United States
Santa Barbara Hematology Oncology Medical Group, Inc. — Santa Barbara, California, United States
University of Colorado Cancer Center — Aurora, Colorado, United States
Rocky Mountain Cancer Centers, LLP — Lakewood, Colorado, United States
Mount Sinai Medical Center — Miami Beach, Florida, United States
Florida Cancer Research Institute — Plantation, Florida, United States
University of Kansas Medical Center Research Institute, Inc. — Westwood, Kansas, United States
Holy Cross Hospital — Silver Spring, Maryland, United States
Henry Ford Medical Center — Novi, Michigan, United States
University of Minnesota — Minneapolis, Minnesota, United States
Mayo Clinic — Rochester, Minnesota, United States
Roswell Park Cancer Institute — Buffalo, New York, United States
Herbert Irving Comprehensive Cancer Center — New York, New York, United States
Weill Cornell Medical College New York Presbyterian Hospital — New York, New York, United States
Eastchester Center for Cancer Care / BRANY — The Bronx, New York, United States
University of Cincinnati Physicians Company, LLC — Cincinnati, Ohio, United States
University Hospitals of Cleveland — Cleveland, Ohio, United States
Erlanger Medical Center — Chattanooga, Tennessee, United States
Texas Oncology, P.A. - Beaumont — Beaumont, Texas, United States
Texas Oncology, P.A. — Dallas, Texas, United States
UT Southwestern Medical Center — Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center — Houston, Texas, United States
Millennium Oncology — Houston, Texas, United States
Texas Health Physicians Group — Plano, Texas, United States

Full record on ClinicalTrials.gov

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