Study of MLN2480 in Participants With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Participants With Metastatic Melanoma
Condition: Melanoma; Metastatic Melanoma; Solid Tumor; Neoplasm
MeSH terms: Melanoma
Intervention: MLN2480
Intervention description: Dose Escalation Phase: participants will receive MLN2480 orally in escalating doses every other day or once weekly for three weeks of a 28-day cycle. Participants may continue treatment for additional cycles (up to 12 months) until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. If it is determined that a participant would derive benefit from continued therapy beyond 12 months treatment may continue. Dose Expansion Phase: Participants will take MLN2480 at the maximum tolerated dose orally every other day or once weekly for three weeks of a 28-day cycle until disease progression, unacceptable toxicity, or the participant discontinues for any other reason. The maximum duration of treatment is 1 year unless determined that a participant would derive benefit from continued therapy beyond 12 months.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 149.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      This is a phase 1, multicenter, nonrandomized, open-label, dose escalation study. The study
      will be conducted in 2 stages, Dose Escalation and Dose Expansion. The Dose Escalation phase
      will include participants with solid tumors (including melanoma) who have failed or are not
      candidates for standard therapies or for whom no approved therapy is available. The Dose
      Expansion phase will include participants with metastatic melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent.

          2. Male or female participants 18 years or older.

          3. Dose Escalation phase: Participants with solid tumors (including melanoma) who have
             failed or are not candidates for standard therapies of for whom no approved therapy is
             available.

          4. Dose Expansion phase: Metastatic melanoma (locally advanced or metastatic melanoma).

          5. Dose Expansion phase: At least 1 measurable lesion which has not been treated
             previously with radiotherapy. A newly arising lesion in a previously irradiated field
             is acceptable.

          6. For participants undergoing biopsy procedures: Prothrombin time (PT) and activated
             partial thromboplastin time (aPTT) must be within the normal range.

          7. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             (<=) 1.

          8. Adequate tissue sample from either archival formalin-fixed paraffin-embedded (FFPE)
             tumor tissue or new biopsy of tumor.

          9. Previous chemotherapy, immunotherapy, and hormone therapy must be completed at least 4
             weeks prior to the administration of MLN2480 and radiation must be completed at least
             3 weeks prior to the administration of MLN2480; all associated toxicity must be
             resolved to <=Grade 1.

         10. Expected survival time of at least 3 months in the opinion of the investigator.

         11. Participants who do not have hypo- or hyperthyroidism.

         12. Ability to swallow and retain oral medication.

         13. Female participants who are postmenopausal for at least 1 year, surgically sterile, or
             agree to practice 2 effective methods of contraception through 3 months after the last
             dose of study drug or agree to practice true abstinence.

         14. Male participants who, even if surgically sterilized, agree to practice effective
             barrier contraception through 3 months after the last dose of alisertib or agree to
             practice true abstinence.

        Exclusion Criteria

          1. History of any major disease that might interfere with safe protocol participation.

          2. Dose Expansion phase: Previous treatment with RAF or MEK inhibitors.

          3. Laboratory values as specified in study protocol.

          4. Current enrollment in any other investigational treatment study.

          5. Evidence of current uncontrolled cardiovascular conditions within the past 6 months.

          6. Prior investigational agents for malignant or non-malignant disease within 4 weeks
             prior to Day 1.

          7. Active hepatitis or human immunodeficiency virus (HIV) infection.

          8. Active bacterial or viral infection.

          9. Female participants who are pregnant or currently breastfeeding.

         10. Major surgery within 28 days of Day 1.

         11. Refractory nausea and vomiting, malabsorption, or significant bowel or stomach
             resection.

         12. Inability to comply with study requirements.

         13. Other unspecified reasons that, in the opinion of the investigator or Millennium, make
             the participant unsuitable for enrollment.