Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma
Condition: Nonhematologic Malignancies; Lymphoma
MeSH terms: Lymphoma; Neoplasms
Intervention: Ixazomib 2.5 mg; Ixazomib 4 mg Capsule A; Ixazomib 4 mg Capsule B; Ketoconazole; Rifampin; Clarithromycin; Ixazomib 4 mg Capsule B
Intervention description: Ixazomib 2.5 mg Capsule B (Cycle 1 only); Ixazomib 4 mg Capsule A (Cycle 1 only); Ixazomib 4 mg Capsule B (Cycle 2 and beyond ); Ketoconazole 400 mg tablets (Cycle 1 only); Rifampin 600 mg capsule (Cycle 1 only); Clarithromycin 500 mg tablets (Cycle 1 only); Ixazomib 4 mg Capsule B (Cycle 1 and beyond)
Intervention MeSH terms: Clarithromycin; Rifampin; Ketoconazole; Ixazomib; Glycine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 112.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cmax: maximum plasma concentration; AUC0-tlast: area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

Summary:

      This is an open-label, multicenter, sequential, 5-arm, phase 1 study of oral IXAZOMIB
      designed to assess drug-drug interaction with ketoconazole (Arm 1), the relative
      bioavailability of 2 capsule formulations of IXAZOMIB (Arm 2), food effect (Arm 3), drug-drug
      interaction with rifampin (Arm 4), and drug-drug interaction with clarithromycin (Arm 5) in
      participants with advanced nonhematologic malignancies or lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participants 18 years or older.

          -  Participants must have a diagnosis of histologically or cytologically confirmed
             metastatic and/or advanced solid tumor malignancy or lymphoma for which no effective
             standard treatment is available.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          -  Female participants who are postmenopausal at least 1 year, or surgically sterile, or
             if of childbearing potential, agree to practice 2 effective methods of contraception,
             at the same time from the time of signing the consent form through 90 days after the
             last dose of study drug, or agree to practice true abstinence.

          -  Male participants, even if surgically sterilized, agree to practice effective barrier
             contraception during the entire study treatment period and through 90 days after the
             last dose of study drug or agree to practice true abstinence.

          -  Voluntary written informed consent.

          -  Clinical laboratory values as specified in protocol.

          -  Suitable venous access.

          -  Recovered (that is, less than [< ] Grade 1 toxicity or participant's baseline status)
             from the reversible effects of prior anticancer therapy.

        Exclusion Criteria:

          -  Peripheral neuropathy greater than (>) Grade 2 on clinical examination.

          -  Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2, strong
             inhibitors of CYP3A, or strong CYP3A inducers or use of ginkgo biloba or St. John's
             wort within 14 days before the first dose of IXAZOMIB.

          -  Participant has symptomatic brain metastasis. Participants with brain metastases must:
             have stable neurologic status following surgery or radiation for at least 2 weeks
             after completion of the definitive therapy; and be without neurologic dysfunction that
             would confound the evaluation of neurologic and other adverse events.

          -  Female participants who are pregnant or lactating.

          -  Serious illness that could interfere with protocol completion.

          -  Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior
             allogeneic stem cell transplant at any time.

          -  Prior treatment with rituximab or other unconjugated any antibody treatment within 42
             days (21 days if there is clear evidence of progressive disease or immediate treatment
             is mandated).

          -  Ongoing treatment with corticosteroids.

          -  Radiotherapy within 21 days before the first dose of study drug.

          -  Major surgery within 14 days before the first dose of study drug.

          -  Infection requiring systemic antibiotic therapy or other serious infection within 14
             days prior to first dose of study drug.

          -  Life-threatening illness unrelated to cancer.

          -  Known human immunodeficiency virus (HIV) positive, hepatitis B surface
             antigen-positive, or suspected hepatitis C infection.

          -  Diagnosis or treatment of another malignancy within 2 years preceding first dose, or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type
             are not excluded if they have undergone complete resection.

          -  Evidence of uncontrolled cardiovascular conditions.

          -  QTc > 500 milliseconds on a 12-lead electrocardiogram (ECG).

          -  Known gastrointestinal disease or procedure that could interfere with the oral
             absorption or tolerance of IXAZOMIB including difficulty swallowing capsules; diarrhea
             > Grade 1 despite supportive therapy.

          -  Participants with gastric achlorhydria (Arm 1 only).

          -  Participants who have used any nicotine containing products within 14 days before the
             first dose of study drug (Arm 1, Arm 4, and Arm 5).

          -  Treatment with any investigational products or systemic antineoplastic therapies
             within 21 days before the first dose of IXAZOMIB.

          -  Participants with known hypersensitivity to macrolide antibiotics (example,
             clarithromycin, erythromycin, azithromycin) or a history of jaundice/liver injury
             during prior exposure to clarithromycin (Arm 5 only).