Solid Tumors
Conditions
Brief summary
This is a Phase 1 open-label study and consists of 3 treatment groups (dose levels) . Treatment cycles are 3 weeks in duration. The primary objective of this study is to determine the recommended phase two dose (RPTD) of veliparib (ABT-888) when administered in combination with carboplatin and paclitaxel in Japanese subjects with solid tumors. Secondary objectives are to assess pharmacokinetics and to obtain a preliminary efficacy of anti-tumor activity in the subjects.
Interventions
Dosing orally twice daily starting Day 1 through day 7 of each cycle. Decisions to move to the next cohort will be based on evaluation of DLTs in the current cohort. Decisions will be made with a discussion between the Sponsor and the principal investigator to dose escalate or de-escalate or add more subjects to the cohort.
DRUGcarboplatin
Carboplatin will be administered on Day 3 of each cycle, intravenously.
DRUGpaclitaxel
Paclitaxel will be administered on Day 3 of each cycle, intravenously.
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed malignant solid tumor. * Patients who are amenable to standard combination chemotherapy of carboplatin and paclitaxel. * Patients should have received less than or equal to 1 prior chemotherapy regimens for advanced stage disease. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * Patients must have normal organ and marrow function
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or the adverse events due to agents administered more than 3 weeks earlier have not recovered to less than grade 2. * Known history of allergic reactions to carboplatin or cremophor-paclitaxel. * Patients who have previously received a poly(ADP-ribose) polymerase (PARP) inhibitor. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection requiring treatment, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * History of seizure disorder. * Hepatitis B surface antigen (HBsAg) positive, Hepatitis C virus (HCV) antibody positive or Human immunodeficiency virus (HIV)-positive patients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the maximum tolerated dose and recommended Phase two dose | During the first cycle (21 days from first dose of veliparib) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of veliparib (ABT-888) when administered in combination with carboplatin and paclitaxel | Eight timepoints on Day 3 of first cycle (21 days) | — |
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of paclitaxel when administered in combination with veliparib (ABT-888) and carboplatin | Eight timepoints on Day 3 of first cycle (21 days) | — |
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of carboplatin when administered in combination with veliparib (ABT-888) and paclitaxel | Six timepoints on Day 3 of first cycle (21 days) | — |
| Preliminary tumor response | From date of first dose of veliparib until the date of first documented progression or date of death from any cause, whichever come first, assessed up to 6 cycles. | Computerized tomography (CT) scan of chest, abdomen and pelvis to assess tumor burden |
| Pharmacokinetics; Area Under the Curve (AUC), Maximum observed plasma concentration (Cmax) and Time to Cmax (Tmax) of veliparib (ABT-888) | Eight timepoints on Day 1 of first cycle (21 days) | — |
| Safety assessment; Clinical lab testings | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | Hematology, Chemistry and Urinalysis |
| Safety assessment; Adverse event monitoring | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | Collect all adverse events at each visit |
| Safety assessment; Change from Baseline in Electrocardiogram (ECG) | Day 8 of first cycle (21 days) | — |
| Safety assessment; Physical exam including vital signs | From date of first dose of veliparib until 30 days after last dose of veliparib (up to 6 cycles) | Blood pressure, pulse and body temperature |
Countries
Japan
Outcome results
None listed