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MLN0128 in Combination With Fulvestrant in Women With Advanced or Metastatic Breast Cancer After Aromatase Inhibitor Therapy

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ClinicalTrials.gov Identifier: NCT02756364
Recruitment Status : Active, not recruiting
First Posted : April 29, 2016
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The primary purpose of this study is to compare the progression free survival (PFS) of participants treated with the combination of fulvestrant plus daily MLN0128 and fulvestrant plus weekly MLN0128 versus participants treated with single-agent fulvestrant.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Fulvestrant Drug: MLN0128 Phase 2

Detailed Description:

The drug being tested in this study is called MLN0128. MLN0128 is being tested to treat postmenopausal women with advanced or metastatic estrogen receptor (ER) positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer that has progressed during or after aromatase inhibitor (AI) therapy. This study will evaluate the efficacy and safety of combination of fulvestrant + daily MLN0128 and fulvestrant + weekly MLN0128 compared with fulvestrant alone.

The study will enroll approximately 153 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups—which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

  • Fulvestrant 500 mg
  • Fulvestrant 500 mg + MLN0128 4 mg
  • Fulvestrant 500 mg + MLN0128 30 mg

All participants will receive either fulvestrant 500 mg intramuscularly (IM), fulvestrant 500 mg + MLN0128 4 mg daily or fulvestrant 500 mg + MLN0128 30 mg weekly.

This multicenter trial will be conducted worldwide. Participants will make multiple visits to the clinic, and end of treatment (EOT) visit which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for progression free survival (PFS) and overall survival (OS).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase 2 Study of MLN0128 (A TORC1/2 Inhibitor) in Combination With Fulvestrant in Women With ER-Positive/HER2-Negative Advanced or Metastatic Breast Cancer That Has Progressed During or After Aromatase Inhibitor Therapy
Actual Study Start Date : June 1, 2016
Estimated Primary Completion Date : October 22, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arm Intervention/treatment
Active Comparator: Fulvestrant 500 mg
Fulvestrant 500 mg, intramuscularly (IM), once on Cycle 1 Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle until progressive disease, unacceptable toxicity, or withdrawal of consent.
Drug: Fulvestrant
Fulvestrant IM injection

Experimental: Fulvestrant 500 mg + MLN0128 4 mg
Fulvestrant 500 mg, IM, once on Cycle 1 Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle along with MLN0128 4 mg, capsule, orally, once daily of a 28-day treatment cycle until progressive disease, unacceptable toxicity, or withdrawal of consent.
Drug: Fulvestrant
Fulvestrant IM injection

Drug: MLN0128
MLN0128 capsule

Experimental: Fulvestrant 500 mg + MLN0128 30 mg
Fulvestrant 500 mg, IM, once on Cycle 1 Days 1 and 15, and then on Day 1 of each subsequent 28-day cycle along with MLN0128 30 mg, capsule, orally, once weekly of a 28-day treatment cycle until progressive disease, unacceptable toxicity, or withdrawal of consent.
Drug: Fulvestrant
Fulvestrant IM injection

Drug: MLN0128
MLN0128 capsule




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 23 Months ]

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 23 Months ]
  2. Time to Progression (TTP) [ Time Frame: Up to 23 Months ]
  3. Objective Response Rate (ORR) [ Time Frame: Up to 23 Months ]
  4. Clinical Benefit Rate (CBR) [ Time Frame: Up to 23 Months ]
  5. Percentage of Participants who Experience at Least One Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to 23 Months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female participants aged 18 years or older who are postmenopausal.
  2. Histologically proven diagnosis of breast cancer with evidence of metastatic disease or locoregional recurrence. 3. Histological confirmation and documentation of estrogen receptor (ER)-positive status (≥1% positive stained cells). 4. Histological or cytological confirmation and documentation of human epidermal growth factor receptor-2 (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.
  3. Measureable disease
  4. Progressive Disease (PD) during prior aromatase inhibitor (AI) therapy.
  5. Have a history of brain metastasis 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.
  6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
  7. 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) ≥1.5*10^9/L; platelet count ≥100*10^9/L; hemoglobin (Hgb) ≥9 g/dL.
    • Total bilirubin ≤1.5*the upper limit of the normal range (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5*ULN (≤5*ULN if liver metastases are present).
    • Creatinine clearance ≥40 mL/min based 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.

Exclusion Criteria:

  1. Prior therapy with mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), or dual PI3K-mTOR inhibitors, serine/threonine-specific protein kinase (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 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).
  5. Poorly controlled diabetes mellitus defined as hemoglobin A1c (glycosylated hemoglobin; HbA1c) >7%; participants with a history of transient glucose intolerance due to corticosteroid administration may be eligible if all other inclusion/exclusion criteria are met.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02756364


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Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02756364     History of Changes
Other Study ID Numbers: C31006
2015-003612-20 ( EudraCT Number )
U1111-1174-2165 ( Registry Identifier: WHO )
First Posted: April 29, 2016    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action