Advanced Solid Tumors
Conditions
Keywords
PARP Inhibitors
Brief summary
The purpose of this study is to determine the maximum tolerated dose of veliparib (ABT-888)and to establish the recommended Phase 2 dose of veliparib (ABT-888) when administered in combination with carboplatin and gemcitabine in subjects with advanced solid tumors.
Interventions
Dosing orally twice daily starting Cycle 2 Day 1- through 21 adjusted for subsequent cohorts using a continuous reassessment method.
DRUGcarboplatin
Carboplatin will be dosed on Day 1 of each cycle, intravenously.
DRUGgemcitabine
Dosing on Days 1 and 8 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
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed solid tumors that are metastatic or unrespectable for which carboplatin/gemcitabine is a treatment option. * Eastern Cooperative Group performance score of 0 to 2. * Adequate hematologic, hepatic and renal function * Subject has received up to 2 DNA damaging or cytotoxic regimens in the past five years
Exclusion criteria
* Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within 28 days prior to study administration. * Subjects with known history of brain metastases and primary CNS tumors. * Hypersensitivity reactions to platinum compounds or gemcitabine. * Clinically significant and uncontrolled major medical conditions * Active malignancy within the past 5 years except for any cancer in situ cured or non-melanoma carcinoma of the skin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the maximum tolerated dose and recommended Phase 2 dose | ABT-888 will be dose escalated until the largest dose is reached based on the probability of dose, limiting toxicities is based per continual reassessment method (CRM). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety assessment: Electrocardiogram | Screening, Day 8 of each Cycle of drug and Final Visit | — |
| Safety assessment: Clinical Laboratory Tests | Screening, Day 1 and Day 8 of each cycle, Final Visit and 30 Day Follow-up Visit | Hematology and Chemistry |
| Pharmacokinetics Area Under the Curve (AUC) | Timepoints: 30 and 45 minutes, 1,1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5,6,6.5, 7 and 8 hours past dose | — |
| Safety assessment: Adverse event assessments | All study visits | Collect all adverse events at each visit |
| Tumor assessment | Screening, every nine weeks and Final Visit | Computerized tomography (CT) scan of chest, abdomen and pelvis to assess tumor burden |
| Physical exam including vital signs | Screening, Cycle 1 Day 8, Day 1 of all cycles starting with Cycle2, Final Visit and 30 Day Follow-up Visit | Physical exam including blood pressure, pulse and temperature |
Outcome results
None listed