Clinical trial NCT01912222: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Hematologic Malignancies
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-31
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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
timeFrame: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
measure: Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
timeFrame: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
measure: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
timeFrame: Part A, Day 1: Pre-dose and at multiple timepoints (up to 336 hours) post-dose
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
timeFrame: 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])
measure: Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values
timeFrame: Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)
measure: Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs
timeFrame: Baseline up to Day 15 for each treatment cycle (28 days treatment cycle for up to a maximum of 12 cycles)
Secondary outcomes:
Other outcomes:
Locations:
city: Fairway
country: United States
state: Kansas
city: Cleveland
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: