Phase 1 N=48 Treatment

Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction

Advanced Solid Tumors · Hematologic Malignancies

Bottom Line

View on ClinicalTrials.gov: NCT01912222 ↗

Enrolled (actual)

Serious AEs

64.6%

Results posted

Mar 2016

Primary outcome: Primary: 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 — 9.6476; 7.3292; 4.4383 nanogram*hours per milliliter (ng*hr/mL)

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: IXAZOMIB (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Millennium Pharmaceuticals, Inc.
Primary completion: Mar 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY 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	9.6476; 7.3292; 4.4383	—
PRIMARY Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib	0.50893; 0.37245; 0.23176	—
PRIMARY Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib	0.950; 1.500; 1.205	—
PRIMARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)	13; 15; 20; 6; 10; 15	—
PRIMARY Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values	0; 0; 0	—
PRIMARY Number of Participants Reporting Clinically Significant Change From Baseline in Vital Signs	0; 0; 0	—

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01912222). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.