Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01912222
• Other study ID #: C16018
• Status: Completed
• Phase: Phase 1
• First received: July 26, 2013
• Last updated: April 23, 2015
• Start date: August 2013
• Est. completion date: February 2015

Study information

• Verified date: April 2015
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 or severe hepatic impairment) as defined by the National Cancer Institute (NCI) Organ Dysfunction Working Group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 liver 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

• Any cardiovascular condition specified in the study protocol

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Hematologic Malignancies
• Neoplasms

Intervention

Drug:
• IXAZOMIB

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last)	IXAZOMIB in plasma	Days 1 to 15 of Part A	No
Primary	Maximum (peak) concentration (Cmax)	IXAZOMIB in Plasma	Days 1 to 15 of Part A	No
Primary	Number of adverse events	Safety and tolerability of IXAZOMIB.	From first dose of study drug through 30 days after the last dose of study drug	Yes