Clinical Trials /

Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer

NCT02719691

Description:

This is a phase Ib study designed to evaluate the safety and toxicity of the combination of Alisertib and MLN0128 in patients with advanced solid tumors with an expansion cohort in patients with previously treated metastatic TNBC.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Phase I Study of <span class="go-doc-concept go-doc-intervention">MLN0128</span> and <span class="go-doc-concept go-doc-intervention">MLN8237</span> in Patients With Advanced Solid Tumors and Metastatic <span class="go-doc-concept go-doc-keyword">Triple-negative</span> Breast Cancer

Title

  • Brief Title: Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer
  • Official Title: A Phase Ib Study of the Combination of MLN0128 (Dual TORC1/2 Inhibitor) and MLN8237 (Aurora A Inhibitor, Alisertib) in Patients With Advanced Solid Tumors With an Expansion Cohort in Metastatic Triple-negative Breast Cancer (TNBC)
  • Clinical Trial IDs

    NCT ID: NCT02719691

    ORG ID: 15-1135.cc

    Trial Conditions

    Metastatic Breast Cancer

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    Alisertib Dual TORC1/2 Inhibitor Dose-Escalation of Alisertib and MLN0128, Dose-Expansion of Alisertib and MLN0128
    MLN0128 MLN8237 (Aurora A inhibitor) Dose-Escalation of Alisertib and MLN0128, Dose-Expansion of Alisertib and MLN0128

    Trial Purpose

    This is a phase Ib study designed to evaluate the safety and toxicity of the combination of
    Alisertib and MLN0128 in patients with advanced solid tumors with an expansion cohort in
    patients with previously treated metastatic TNBC.

    Detailed Description

    The purpose of this study is to evaluate the combination of Alisertib and MLN0128 in
    patients with advanced solid tumors refractory to standard treatment followed by an
    expansion cohort of patients with metastatic TNBC with exploratory correlative studies.

    Trial Arms

    Name Type Description Interventions
    Dose-Escalation of Alisertib and MLN0128 Experimental This group will receive a Dose-Escalation: Combination of MLN0128 and Alisertib using a standard 3 + 3 design. The starting dose of Alisertib is 30 mg given PO twice daily (BID) Days 1-7 repeat every 21 days. The starting dose for MLN0128 is 1 mg given by mouth (PO) once daily with continuous dosing. Alisertib, MLN0128
    Dose-Expansion of Alisertib and MLN0128 Experimental Group 1: This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, single agent Alisertib will be administered at the MTD on days 1-7 and MLN0128 will be administered on days 8-21. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21. Group 2: This group will receive a Dose-Expansion of Alisertib and Dose-Expansion of MLN0128. In cycle 1, MLN0128 will be administered at the MTD days 1-28 and Alisertib will be administered at the MTD on days 8-15. In cycle 2 and beyond, dosing with both agents will begin on day 1, with Alisertib administered days 1-7 and MLN0128 administered days 1-21. Alisertib, MLN0128

    Eligibility Criteria

    Inclusion Criteria:

    1. Male or female patients 18 years or older.

    2. Dose Escalation Cohort: Patients must have a diagnosis of a histologically confirmed
    solid tumor that is incurable and refractory to standard therapy or for which no
    standard therapy exists.

    3. TNBC Dose Expansion Cohort: Patients must have a diagnosis of histologically
    confirmed metastatic TNBC defined as negative for estrogen receptor, progesterone
    receptor and human epidermal growth factor 2 (HER2). Patients must have received
    either adjuvant or first line chemotherapy for metastatic disease.

    4. Dose Expansion Cohort: At least one tumor lesion amenable to repeat core needle
    biopsy or punch biopsy without unacceptable risk of a major procedural complication.

    5. Eastern Cooperative Oncology Group (ECOG) performance status < 1.

    6. Three weeks or 5 half-lives from previous systemic anticancer therapy.

    7. All acute treatment-related toxicities from prior therapy must have resolved to Grade
    < 1 prior to study entry excluding alopecia.

    8. For women:

    - Postmenopausal for at least 1 year before the screening visit, OR

    - Surgically sterile, OR

    - If they are of childbearing potential, agree to practice 2 effective methods of
    contraception.

    For men:

    Agree to practice effective barrier contraception during the entire study treatment
    period and through 120 days after the last dose of study drug.

    9. Patients must meet screening laboratory values.

    10. Left ventricular ejection fraction (LVEF) > lower limit of normal (LLN) of the
    institutional standard of normal as measured by echocardiogram (ECHO) or multiple
    gated acquisition scan (MUGA) within 4 weeks prior to first study drug
    administration.

    11. Ability to swallow oral medications.

    12. Voluntary written consent must be given before 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.

    13. Patients who have a history of brain metastasis are eligible for the study provided
    they meet certain criteria.

    Exclusion Criteria:

    1. Other clinically significant co-morbidities.

    2. Known human immunodeficiency virus infection.

    3. Radiation therapy to more than 25% of the bone marrow.

    4. Known history of uncontrolled sleep apnea syndrome and other conditions that could
    result in excessive daytime sleepiness.

    5. Systemic infection requiring IV antibiotic therapy within 14 days preceding the first
    dose of study drug, or other severe infection.

    6. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
    infection.

    7. Any serious medical or psychiatric illness.

    8. Diagnosed or treated for another malignancy within 2 years before administration of
    the first dose of study drug, or previously diagnosed with another malignancy and
    have any evidence of residual disease. Patients with non-melanoma skin cancer or
    carcinoma in situ of any type are not excluded if they have undergone complete
    resection.

    9. Breast feeding or pregnant.

    10. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI
    disease, or for an unknown reason that may alter the absorption of MLN0128. In
    addition, patients with enteric stomata are also excluded.

    11. Treatment with any investigational products within 3 weeks before the first dose of
    study drug.

    12. History of any of the following within the last 6 months before administration of the
    first dose of the 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 (NYHA) Class III or IV heart failure

    - Pulmonary embolism

    13. Significant active cardiovascular or pulmonary disease.

    14. Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4,
    CYP2C19 or CYP2C19 within 1 week preceding the first dose of study drug.

    15. Patients receiving systemic corticosteroids within 1 week before administration of
    the first dose of study drug.

    16. Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI
    within 7 days before receiving the first dose of study drug

    17. For patients undergoing serial tumor biopsies, known bleeding diathesis or history of
    abnormal bleeding or require anti-coagulation therapy which cannot be interrupted for
    biopsy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 101 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Determine the maximum tolerated dose (MTD) in the combination of MLN0128 and Alisertib in patients with advanced solid tumors measured by treatment adverse events as assessed by the CTCAE v4.03

    Secondary Outcome Measures

    Number of patients that experience an adverse event from MLN0128 and Alisertib in combination measured by treatment adverse events as assessed by the CTCAE v4.03

    Trial Keywords

    MLN0128

    Dual TORC1/2 Inhibitor

    MLN8237

    Aurora A inhibitor

    Alisertib

    Triple-Negative Breast Cancer