Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors; Lymphoma

Treatments: Drug: IXAZOMIB

Study type: Interventional

Funder types: Industry

Identifiers

NCT01953783

C16016

Details and patient eligibility

About

This is a phase 1, 2-part, open-label study in 4 to 6 pharmacokinetic-evaluable participants with advanced solid tumors or lymphoma.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

• 18 years or older
• Histologic or cytologic diagnosis of advanced or metastatic solid tumor or lymphoma for which no standard, curative, or life-prolonging therapies exist or are effective
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time during the entire study through 90 days after the last dose of study drug OR agree to practice true abstinence
• Male participants who agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR agree to practice true abstinence
• Voluntary written consent
• Suitable venous access for the conduct of blood sampling
• Recovered from the reversible effects of prior anticancer therapy

Exclusion criteria

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

• Female participants who are lactating or breastfeeding or have a positive serum pregnancy test
• Serious medical or psychiatric illness that could interfere with the study
• Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug
• Peripheral neuropathy greater than (>) Grade 2
• Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
• Symptomatic brain metastasis. Participants with brain metastases: must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
• Ongoing treatment with corticosteroids
• Major surgery within the 14 days preceding the first dose of study drug
• Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug
• Life-threatening illness unrelated to cancer
• Known hepatitis B surface antigen -positive, or known or suspected active hepatitis C infection or human immunodeficiency virus (HIV) positive
• Diagnosed or treated for another malignancy within 2 years before the 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
• Any cardiovascular condition specified in the study protocol
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB
• History of urinary and/or fecal incontinence
• Inability to comply with study procedures or visit schedule including the requirement for inpatient confinement

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

7 participants in 1 patient group

IXAZOMIB

Experimental group

Description:

Part A: Participants will receive a single dose of 4.1-milligram (mg) \[14C\]-IXAZOMIB oral solution containing approximately 500-nCurie (nCi) of total radioactivity on Day 1 and remain at the clinic for 8 days. On Days 14 and 21, participants may be administered a single 4.0-mg capsule of IXAZOMIB. Participants will return to the clinic in the evening before Days 14, 21, 28, and 35 for a 24-hour overnight clinic visit. Part B: Eligible participants from Part A may continue into Part B once they have completed their Day 35 assessments in Part A. Participants may receive IXAZOMIB capsules administered orally at a dose of 4.0-mg once weekly on Days 1, 8, and 15 of 28-day cycles. Participants will continue in this study until disease progression or unacceptable toxicity.

Treatment:

Drug: IXAZOMIB