Skip to main content
OpenTrials
Completed

NCT Number: NCT01953783

Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

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

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cleveland, Ohio, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ixazomib

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.

Primary outcomes

  1. Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve.

  2. Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

    Time to reach the maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve.

  3. Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose

    AUC(0-312) is a measure of the area under the plasma concentration time-curve from time zero to 312 hrs post-dose for ixazomib.

  4. Part A: Cmax: Maximum Observed Plasma Concentration of TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Maximum observed plasma concentration (Cmax) of TRA is the peak plasma concentration of TRA, obtained directly from the plasma TRA concentration-time curve.

  5. Part A: Tmax: Time to Reach the Cmax for TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Time to reach the maximum observed plasma concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the plasma TRA concentration-time curve.

  6. Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

    AUC(0-816) is a measure of the area under the plasma concentration time-curve from time zero to 816 hrs post-dose for TRA.

  7. Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Maximum observed whole blood concentration (Cmax) of a TRA is the peak whole blood concentration of TRA, obtained directly from the whole blood TRA concentration-time curve.

  8. Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Time to reach the maximum observed whole blood concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the whole blood TRA concentration-time curve.

  9. Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

    AUC(0-816) is a measure of the area under the whole blood concentration time-curve from time zero to 816 hrs post-dose for TRA.

  10. Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine

    Time frame: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose

    Percentage of the ixazomib dose excreted unchanged in the urine from 0 to 168 hrs post-dose.

  11. Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Percentage of the TRA dose excreted in feces from Day 1 to Day 35 of Part A

  12. Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine

    Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

    Percentage of the TRA dose excreted in urine from Day 1 to Day 35 of Part A.

  13. Part A: Renal Clearance of Ixazomib

    Time frame: Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose

    Renal clearance is the volume of plasma from which ixazomib is completely removed by the kidney in a given amount of time, calculated as the amount of ixazomib excreted in the urine divided by the area under the plasma ixazomib concentration-time curve.

Secondary outcomes

  1. Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma

    Time frame: Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose

    The plasma samples were pooled for participants over 816 hrs post-dose, and data was analysed using the Hamilton method time-proportional pooling, and therefore the data is reported as "percent of total radioactivity in plasma" with measure type as "number" and measure dispersion as "Not applicable, NA".

  2. Ixazomib and Metabolites as Percent of Total Dose Administered in Urine

    Time frame: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

    The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled urine. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".

  3. Ixazomib and Metabolites as Percent of Total Dose Administered in Feces

    Time frame: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

    The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled feces. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".

  4. Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: Baseline up to Cycle 5 Day 45

  5. Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values

    Time frame: Baseline up to Cycle 5 Day 45

  6. Number of Participants With TEAEs Related to Vital Signs

    Time frame: Baseline up to Cycle 5 Day 25

    Vital signs included oral body temperature, heart rate, and blood pressure.

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1 Study of [ 14 C]-Ixazomib to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients With Advanced Solid Tumors or Lymphoma

Important dates

Study start
2014
Primary completion
2014
Study completion
2016
First posted
Oct 1, 2013
Registry last updated
Aug 26, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.