A Phase 1 Study of IXAZOMIB in Adult Patients With Advanced Nonhematologic Malignancies
Condition: Advanced Non-hematologic Malignancies
MeSH terms: Neoplasms
Intervention: IXAZOMIB
Intervention description: All participants will receive IXAZOMIB IV injection on Days 1, 4, 8, and 11 of each treatment cycle followed by a rest period of 10 days.
The first stage of the study will be initiated at a starting dose of 0.125 mg/m^2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established.
Intervention MeSH terms: Ixazomib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      This is an open-label, multicenter, phase 1, dose escalation study of IXAZOMIB. The primary
      purpose of this study is to determine the safety profile, establish the maximum tolerated
      dose, and inform the phase 2 dose of IXAZOMIB administered intravenously in participants with
      nonhematologic malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

        Each participant must meet all of the following inclusion criteria to be enrolled in the
        study:

          1. Male or female participants 18 years or older.

          2. Eastern Cooperative Oncology Group performance status 0-2.

          3. A diagnosis of a nonhematologic malignancy for which standard treatment is no longer
             effective. In the expanded cohort, enrollment will be limited to participants with a
             diagnosis of NSCLC, H&N cancer (squamous cell cancer), STS, or PC.

          4. Suitable venous access for pharmacokinetic (PK) and pharmacodynamic evaluations.

          5. Female participants who are post menopausal, surgically sterile, or agree to practice
             2 effective methods of contraception or abstain from heterosexual intercourse.

             Male participants who agree to practice 2 effective methods of contraception or
             abstain from heterosexual intercourse.

          6. Voluntary written consent must be obtained.

          7. Adequate clinical laboratory values during the screening period.

          8. In the escalation portion of the study, radiographically or clinically evaluable tumor
             was required, but measurable disease as defined by response evaluation criteria in
             solid tumors (RECIST) criteria was not required. In the MTD disease expansion cohorts
             and the TPEC, clinically measurable disease as defined by RECIST criteria was required
             for evaluation of NSCLC, H&N cancer, and STS. Prostate specific antigen (PSA) alone
             was acceptable for evaluation of PC.

          9. For participants in the TPEC, tumor tissue that, in the opinion of the investigator,
             could have been safely biopsied using a core needle.

        Exclusion Criteria:

        Participants meeting any of the following exclusion criteria are not to be enrolled in the
        study:

          1. Peripheral neuropathy greater than or equal to (>=) Grade 2.

          2. Female participants who are lactating or have a positive serum pregnancy test during
             the screening period.

          3. Major surgery within 14 days before the first dose of treatment.

          4. Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before the first dose of study treatment.

          5. Life-threatening illness unrelated to cancer.

          6. Diarrhea greater than (>) Grade 1 based on the National Cancer Institute Common
             Terminology .Criteria for Adverse Events (NCI CTCAE) categorization.

          7. Systemic antineoplastic therapy / or radiotherapy within 21 days before the first dose
             of study treatment.

          8. Systemic treatment with prohibited medications.

          9. Participant has symptomatic brain metastasis.

         10. Evidence of current uncontrolled cardiovascular conditions, including cardiac
             arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within
             the past 6 months.

         11. QTc >470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the
             screening period.

         12. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.

         13. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

         14. Treatment with any investigational products within 28 days before the first dose of
             study treatment.

         15. For participants in the TPEC and participants in the MTD disease expansion cohorts who
             gave informed consent to undergo tumor biopsy, ongoing anticoagulant therapy (example,
             aspirin, clopidogrel [Plavix ®], warfarin, or heparin) that cannot be held to permit
             tumor biopsy .

         16. Known allergy to boron or excipients.