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Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction

Primary Purpose

Advanced Solid Tumors, Hematologic Malignancies

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IXAZOMIB
Sponsored by
Millennium Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 18 years or older
  • Patients must have a diagnosis of an advanced malignant solid tumor or hematologic malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective
  • Total bilirubin and aspartate aminotransferase (AST) levels consistent with normal hepatic function (total bilirubin and AST ≤ the upper limit of normal), moderate hepatic impairment (total bilirubin > 1.5 to 3x the upper limit of normal with any AST level) or severe hepatic impairment (total bilirubin > 3x the upper limit of normal with any AST level)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Female patients 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 patients 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
  • Appropriate clinical laboratory values as specified in the protocol

Exclusion Criteria:

  • 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
  • Use of any nicotine-containing products within 14 days before the first dose of study drug
  • Central Nervous System Involvement or Symptomatic brain metastasis. Patients 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 AEs
  • Female patients who are lactating or breastfeeding or have a positive serum pregnancy test
  • Serious medical or psychiatric illness that could interfere with participation in the study
  • Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug
  • Systemic anticancer therapy within 14 days before the first dose of study drug
  • Exposure to nitrosoureas or mitomycin C within 6 weeks before the first dose of study drug
  • Treatment with therapeutic monoclonal antibodies or antibody-drug conjugates within 60 days before the first dose of study drug
  • Radiotherapy or 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
  • Severe CNS, pulmonary, or renal disease not related to the patient's cancer
  • Known human immunodeficiency virus (HIV) positive
  • Evidence of uncontrolled cardiovascular conditions
  • QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB
  • Known allergy to the study medication, its analogues, or excipients in the formulation

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

IXAZOMIB Arm 1

IXAZOMIB Arm 2

IXAZOMIB Arm 3

Arm Description

Experimental: Arm 1 (Normal hepatic function) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 4 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle

Experimental: Arm 2 (Moderate hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 2.3 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle

Experimental: Arm 3 (Severe hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 1.5 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle

Outcomes

Primary Outcome Measures

Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs
Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).

Secondary Outcome Measures

Full Information

First Posted
July 26, 2013
Last Updated
May 3, 2016
Sponsor
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01912222
Brief Title
Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction
Official Title
A Phase 1 Pharmacokinetic Study of Oral IXAZOMIB (MLN9708) in Patients With Advanced Solid Tumors or Hematologic Malignancies With Varying Degrees of Liver Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase 1, 2-part, pharmacokinetic study in patients with advanced solid tumors or hematologic malignancies and varying degrees of liver dysfunction (normal function, moderate hepatic impairement or severe hepatic impairment) as defined by the National Cancer Institute (NCI) Organ Dysfunction Working Group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors, Hematologic Malignancies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IXAZOMIB Arm 1
Arm Type
Experimental
Arm Description
Experimental: Arm 1 (Normal hepatic function) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 4 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle
Arm Title
IXAZOMIB Arm 2
Arm Type
Experimental
Arm Description
Experimental: Arm 2 (Moderate hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 2.3 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle
Arm Title
IXAZOMIB Arm 3
Arm Type
Experimental
Arm Description
Experimental: Arm 3 (Severe hepatic impairment) In the 15 day period that constitutes Part A of the trial, patients will receive a single oral 1.5 mg dose of IXAZOMIB capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive IXAZOMIB on Days 1, 8, and 15 of a 28-day cycle
Intervention Type
Drug
Intervention Name(s)
IXAZOMIB
Primary Outcome Measure Information:
Title
Unbound AUC(0-last): Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time Frame
Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
Title
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
Time Frame
Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
Title
Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time Frame
Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
Title
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Description
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame
Baseline up to 30 days after last dose of study drug (Day 45 for each treatment cycle for up to a maximum of 12 cycles [28 days treatment cycles])
Title
Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values
Description
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Time Frame
Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)
Title
Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs
Description
Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Time Frame
Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years or older Patients must have a diagnosis of an advanced malignant solid tumor or hematologic malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective Total bilirubin and aspartate aminotransferase (AST) levels consistent with normal hepatic function (total bilirubin and AST ≤ the upper limit of normal), moderate hepatic impairment (total bilirubin > 1.5 to 3x the upper limit of normal with any AST level) or severe hepatic impairment (total bilirubin > 3x the upper limit of normal with any AST level) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Female patients 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 patients 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 Appropriate clinical laboratory values as specified in the protocol Exclusion Criteria: 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 Use of any nicotine-containing products within 14 days before the first dose of study drug Central Nervous System Involvement or Symptomatic brain metastasis. Patients 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 AEs Female patients who are lactating or breastfeeding or have a positive serum pregnancy test Serious medical or psychiatric illness that could interfere with participation in the study Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug Systemic anticancer therapy within 14 days before the first dose of study drug Exposure to nitrosoureas or mitomycin C within 6 weeks before the first dose of study drug Treatment with therapeutic monoclonal antibodies or antibody-drug conjugates within 60 days before the first dose of study drug Radiotherapy or 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 Severe CNS, pulmonary, or renal disease not related to the patient's cancer Known human immunodeficiency virus (HIV) positive Evidence of uncontrolled cardiovascular conditions QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB Known allergy to the study medication, its analogues, or excipients in the formulation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Fairway
State/Province
Kansas
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction

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