Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

NCT ID: NCT01953783

Last Updated: 2020-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-19
• Study Completion Date: 2016-02-09

Brief Summary

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

Conditions

Advanced Solid Tumors; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IXAZOMIB

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: DRUG

Part A: Ixazomib 4.1 mg containing approximately 500-nCi [14C]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21.

Part B: Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity.

Interventions

IXAZOMIB

Part A: Ixazomib 4.1 mg containing approximately 500-nCi [14C]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21.

Part B: Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Cleveland, Ohio, United States

Countries

United States

References

Gupta N, Zhang S, Pusalkar S, Plesescu M, Chowdhury S, Hanley MJ, Wang B, Xia C, Zhang X, Venkatakrishnan K, Shepard DR. A phase I study to assess the mass balance, excretion, and pharmacokinetics of [14C]-ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2018 Jun;36(3):407-415. doi: 10.1007/s10637-017-0509-1. Epub 2017 Sep 21.

Reference Type: DERIVED

PMID: 28932928 (View on PubMed)

Other Identifiers

C16016

Identifier Type: -

Identifier Source: org_study_id