Clinical trial NCT01953783: Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB
Official title: A Phase 1 Study of [ 14 C]-Ixazomib to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients With Advanced Solid Tumors or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lymphoma
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-10-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
measure: Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose
measure: Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose
measure: Part A: Cmax: Maximum Observed Plasma Concentration of TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: Tmax: Time to Reach the Cmax for TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
measure: Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose
measure: Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine
timeFrame: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose
measure: Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine
timeFrame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose
measure: Part A: Renal Clearance of Ixazomib
timeFrame: Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose
Secondary outcomes:
measure: Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma
timeFrame: Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose
measure: Ixazomib and Metabolites as Percent of Total Dose Administered in Urine
timeFrame: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
measure: Ixazomib and Metabolites as Percent of Total Dose Administered in Feces
timeFrame: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose
measure: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Cycle 5 Day 45
measure: Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values
timeFrame: Baseline up to Cycle 5 Day 45
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: Baseline up to Cycle 5 Day 25
Other outcomes:
Locations:
city: Cleveland
country: United States
state: Ohio
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.