A Study of ABT-165 in Subjects With Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT01946074
- Lead Sponsor
- AbbVie
- Brief Summary
This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-165 when administered as monotherapy and in combination with paclitaxel or 5-fluoruracil, folinic acid and irinotecan (FOLFIRI) or ABBV-181 with/without paclitaxel in subjects with advanced solid tumors. Enrollment to Cohorts A, B were completed and for Cohorts C and D are recruiting.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- Subject must have advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit.
- Subject has adequate bone marrow, renal, hepatic and coagulation function.
- Subject must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or disease evaluable by assessment of tumor antigens including but not limited to cancer antigen (CA-125) and prostate-specific antigen (PSA).
- Women of childbearing potential must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline prior to the first dose of study drug. Female subject considered not of childbearing potential must be documented as being surgically sterile or post-menopausal for at least 1 year. Women of childbearing potential and men must agree to use adequate contraception.
- Subjects in the combination therapy cohorts must meet the above inclusion criteria and be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects in the combination therapy cohorts who are to receive ABBV-181, an anti-PD1 antibody, must also meet other criteria described in the Protocol.
- Subject has received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days or anti-cancer herbal therapy within 7 days prior to Cycle 1 Day 1 of ABT-165.
- Subject has uncontrolled metastases to the central nervous system (CNS).
- Subject has unresolved clinically significant toxicities from prior anticancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher.
- Subject has history (within previous 5 years) of clinically significant pulmonary hypertension, uncontrolled systemic hypertension or hypertensive crisis, symptomatic heart failure, cardiomyopathy, myocardial infarction, unstable/severe angina pectoris, cardiac arrhythmia requiring medication, coronary/peripheral artery bypass graft, aneurysm or aneurysm repair, angioplasty, cerebrovascular accident, transient ischemic attack or the left ventricular ejection fraction (LVEF) less than 50%.
- Subjects enrolled on the combination therapy phase must not meet the above exclusion criteria and must be eligible to receive paclitaxel or FOLFIRI per most current prescribing information, or at the discretion of the Investigator. Subjects receiving ABBV-181 must not meet other exclusion criteria described in the Protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A ABT-165 ABT-165 plus paclitaxel Cohort B FOLFIRI ABT-165 plus FOLFIRI Cohort B ABT-165 ABT-165 plus FOLFIRI Cohort C ABT-165 ABT-165 plus ABBV-181 Monotherapy ABT-165 ABT-165 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle). Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-165 Cohort A paclitaxel ABT-165 plus paclitaxel Cohort C ABBV-181 ABT-165 plus ABBV-181 Cohort D ABBV-181 ABT-165 plus ABBV-181 plus paclitaxel Cohort D ABT-165 ABT-165 plus ABBV-181 plus paclitaxel Cohort D paclitaxel ABT-165 plus ABBV-181 plus paclitaxel
- Primary Outcome Measures
Name Time Method Clinical lab testing Up to 30 days after a 24-month treatment period Hematology, Chemistry, and Urinalysis
The terminal elimination half life of ABT-165 Up to 90 days after a 24-month treatment period Area under the curve (AUC) form time zero to the last measurable concentration AUC (0-t) Up to 90 days after a 24-month treatment period AUC (0-t) = Area under the serum concentration versus time curve form time zero (pre-dose) to the time of the last measurable concentration
Cardiac assessment Up to 30 days after a 24-month treatment period Electrocardiogram (ECG), echocardiogram (ECHO), basic natriuretic peptide (BNP) and troponin I
Physical exam Up to 30 days after a 24-month treatment period Assessment of normal/abnormal physical findings
Maximum observed serum concentration (Cmax) of ABT-165 Up to 90 days after a 24-month of treatment period Number of participants with Adverse Events Up to 90 days after a 24-month treatment period Collect all adverse events at each visit
Vital signs Up to 30 days after a 24-month treatment period Blood pressure, heart rate, respiratory rate and body temperature
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) Up to 30 days after a 24-month treatment period PFS is defined as the time from the first dose date of ABT-165 to either disease progression or death, whichever occurs first
Duration of overall response (DOR) Up to 30 days after a 24-month treatment period DOR is defined as the time from the subject's initial CR or PR to the time of disease progression
Objective response rate (ORR) Up to 30 days after a 24-month treatment period ORR is defined as the proportion of the subjects who have a complete response (CR) or partial response (PR)
Trial Locations
- Locations (10)
HonorHealth Research Institute - Pima /ID# 105677
🇺🇸Scottsdale, Arizona, United States
University of California, Los Angeles /ID# 141389
🇺🇸Los Angeles, California, United States
Scottsdale Healthcare /ID# 105678
🇺🇸Scottsdale, Arizona, United States
Stanford University School of Med /ID# 123758
🇺🇸Stanford, California, United States
Illinois Cancer Care, PC /ID# 151970
🇺🇸Peoria, Illinois, United States
Horizon Oncology Research Center /ID# 138022
🇺🇸Lafayette, Indiana, United States
University of California, Davis Comprehensive Cancer Center /ID# 141164
🇺🇸Sacramento, California, United States
Tennessee Oncology-Nashville Centennial /ID# 143280
🇺🇸Nashville, Tennessee, United States
Duke Cancer Center /ID# 105679
🇺🇸Durham, North Carolina, United States
Mary Crowley Cancer Research /ID# 123757
🇺🇸Dallas, Texas, United States