MLN0128 in Combination With Fulvestrant in Women With Advanced or Metastatic Breast Cancer After Aromatase Inhibitor Therapy.
- Conditions
- Advanced or Metastatic Breast Cancer.MedDRA version: 19.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-003612-20-ES
- Lead Sponsor
- Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 153
1. Female patients aged 18 years or older who are postmenopausal. Postmenopausal is defined
as:
- Aged > or = 55 years and 1 year or more of natural amenorrhea prior to the Screening visit, or
- Aged <55 years and 1 year or more of amenorrhea prior to the Screening visit, with a follicle-stimulating hormone level >40 mIU/mL and an estradiol level of <20 pg/mL, or
- Surgical menopause with bilateral oophorectomy.
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.
2. Histologically proven diagnosis of breast cancer with evidence of metastatic disease or
locoregional recurrence, not amenable to resection or radiation therapy with curative intent.
3. Histological confirmation and documentation of ER-positive status (?1% positive stained cells) by local laboratory testing utilizing an assay consistent with local standards.
4. Histological or cytological confirmation and documentation of HER2-negative status by local laboratory testing using criteria in the American Society of Oncology (ASCO)/College
of American Pathologists (CAP) Clinical Practice Guideline update.
5. Measureable disease defined as:
- At least 1 extra-osseous lesion that can be accurately measured in at least 1 dimension. The lesion must measure ?20 mm with conventional imaging techniques or ?10 mm with spiral CT or MRI, or
- Bone lesions (lytic or mixed [lytic plus sclerotic]) in the absence of measurable disease as defined above.
Note: Patients with sclerotic/osteoblastic bone lesions only, in the absence of measurable disease, are not eligible.
6. PD during prior AI therapy defined as:
- Progression during or within 12 months after completion or discontinuation of adjuvant therapy or
- Progression during or within 1 month after the end of therapy in the metastatic setting.
Note: AI is not required to be the most recent therapy, but progression on AI and
progression on most recent therapy are both required for eligibility.
7. Patients who have a history of brain metastasis are eligible for the study provided that all of the following criteria are met:
- Brain metastases have been treated.
- No evidence of PD for 3 months before the first dose of study drug.
- No hemorrhage after treatment.
- Off dexamethasone treatment for ?4 weeks before the first dose of study drug.
- No ongoing requirement for dexamethasone or anti-epileptic drugs.
8. ECOG performance status of 0 or 1 (refer to Appendix D).
9. Clinical laboratory values as specified below within 4 weeks before the first dose of study drug:
- Bone marrow reserve consistent with absolute neutrophil count (ANC) ?1.5x10^9/L;
platelet count ?100x10^9/L; hemoglobin (Hgb) ?9 g/dL.
- Total bilirubin ?1.5 x the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?2.5xULN (?5xULN if liver metastases are present).
- Creatinine clearance ?40 mL/min based on Cockcroft-Gault estimate (refer to
Appendix E) or based on a 12- or 24-hour urine collection.
- Fasting serum glucose ?130 mg/dL and fasting triglycerides ?300 mg/dL.
10. Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
11. Voluntary written consent must be given by the patient (or the patient?s legally acceptable representative) before performance of any study-related procedure that is not p
1. Prior therapy with mTOR, PI3K, or dual PI3K-mTOR inhibitors, AKT inhibitors, or
fulvestrant.
2. Prior treatment with >1 line of chemotherapy for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent.
3. Experienced recurrent or PD on >2 endocrine therapies for metastatic breast cancer or for locoregional recurrence that was not amenable to resection or radiation therapy with curative intent.
4. Life-threatening metastatic visceral disease (defined as extensive hepatic involvement or symptomatic pulmonary lymphangitic spread). Patients with discrete pulmonary parenchymal metastases are eligible, provided their respiratory function is not compromised as a result of disease.
5. Other clinically significant comorbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could
compromise the patient?s participation in the study.
6. History of any of the following within the last 6 months before the first dose of study drug:
- 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 (see Appendix F).
- Pulmonary embolism.
7. Significant active cardiovascular or pulmonary disease, including:
- Uncontrolled hypertension (ie, either systolic blood pressure >180 mm Hg or 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 QTc (eg, repeated demonstration of QTc interval >480 ms, or
history of congenital long QT syndrome, or torsades de pointes).
8. Diagnosed with or treated for another malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
9. Prior anticancer therapy or other investigational therapy within 2 weeks before the first dose of study drug.
10. Chronic concomitant therapy with bone-targeting agents (eg, bisphos, denosumab) for the prevention of bone metastases. Concomitant treatment with bone-targeting agents is permitted for treatment of osteoporosis or management of existing bone metastases if initiated at least 4 weeks before the first dose of study drug.
11. Treatment with strong cytochrome P450 (CYP) 3A4, CYP2C9, and/or CYP2C19 inhibitors
and/or inducers within 1 week before the first dose of study drug (see Appendix G).
12. Initiation of treatment with systemic corticosteroids (either IV or oral steroids) within 1 week before the first dose of study drug. However, inhale
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method