Dose Escalation Study of MLN0128 in Participants With Advanced Malignancies
Condition: Advanced Solid Malignancies
MeSH terms: Neoplasms
Intervention: MLN0128
Intervention description: MLN0128 capsules
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: The Escalation Phase was sequential and the Expansion Phase was parallel.
Masking: None (Open Label)
Enrollment: 198.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Solid tumors, MLN0128, TORC1/2 inhibitors

Summary:

      This is a Phase I, open label, Dose Escalation study of oral administration of single agent
      MLN0128 in participants with Advanced Malignancies followed by an Expansion Phase in
      participants with renal cell carcinoma, endometrial cancer or urothelial cancer who have
      measurable disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Voluntary written consent

          -  Locally advanced or metastatic solid tumors with the exception of primary brain tumor,
             and have failed standard of care therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Ability to swallow oral medications

          -  For women of child-bearing potential, negative serum or urine pregnancy test within 14
             days prior to the first study drug administration and use of physician-approved method
             of birth control from 30 days prior to 90 days following the last study drug
             administration

          -  Male participants must be surgically sterile or must agree to use physician-approved
             contraception during the study and for 90 days following the last study drug
             administration

          -  Clinical laboratory values as specified in the protocol

        Additionally, to be eligible for the Dose Expansion portion of the study:

          -  Participants must have evidence of measurable disease per response evaluation criteria
             in solid tumors (RECIST) version 1.1 by radiographic techniques or magnetic resonance
             imaging

          -  Participants must have a pathologic diagnosis of advanced or recurrent endometrial
             adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy

          -  Participants must have a pathologic diagnosis of advanced/metastatic urothelial cancer
             (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least
             1 line of prior therapy in the metastatic/unresectable setting

          -  Participants must have a pathologic diagnosis of advanced renal cell carcinoma (RCC),
             with histological or cytological confirmation of RCC and must have failed at least 1
             prior line of anti-vascular endothelial growth factor therapy (VEGF) therapy
             (including but not limited to sunitinib, and/or sorafenib, and/or bevacizumab and/or
             pazopanib, and/or axitinib) and must not have received prior therapy with a target of
             rapamycin complex 1 (TORC1) inhibitor (such as temsirolimus or everolimus); or

          -  Participants must have a pathologic diagnosis of advanced renal cell carcinoma (RCC)
             and must have progressed on treatment with a TORC1 inhibitor (such as temsirolimus or
             everolimus).

        Exclusion Criteria:

          -  Diagnosis of primary brain tumor

          -  Have received prior cancer or other investigational therapy within 2 weeks prior to
             the first administration of study drug

          -  Known impaired cardiac function or clinically significant cardiac disease

          -  Known treatment with systemic corticosteroid within one week prior to the first
             administration of study drug

          -  Diabetes mellitus

          -  Human immunodeficiency virus (HIV) infection

          -  Known active cardiovascular disease condition as specified in protocol

          -  Failed to recover from the reversible effects of prior anticancer therapies

          -  Pregnancy (positive serum or urine pregnancy test) or breast feeding

          -  Malabsorption due to prior gastrointestinal (GI) surgery, GI disease

          -  Other clinically significant co-morbidities

        Please note that there are additional inclusion and exclusion criteria. The study center
        will determine if you meet all of the criteria.

        Site personnel will explain the trial in detail and answer any question you may have if you
        do qualify for the study. You can then decide whether or not you wish to participate. If
        you do not qualify for the trial, site personnel will explain the reasons.