Cancer Solid tumors
Conditions
Interventions
ABT-767 is administrated orally. In the dose escalation phase all the subjects
receive their first dose ABT-767 at day -3 of cycle 1. From day 1 of cycle 1
the subjects will get a daily dose of ABT-
Sponsors
AbbVie B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Subject must be * 18 years of age. * Subjects must have histological or cytological confirmation of locally advanced or metastatic solid tumor, and - a documented BRCA1 or BRCA2 mutation, OR - high grade serous ovarian, fallopian tube, or primary peritoneal cancer. * Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2. * Subjects must have adequate hematologic, renal, and hepatic function as follows: - Bone Marrow: Absolute neutrophil count (ANC * 1,500/mm3 (1.5 × 109/L); Platelets * 100,000/mm3 (100 × 109/L); Hemoglobin * 9.0 g/dL (1.4 mmol/L) (hemoglobin unsupported by transfusion. - Subject has adequate renal function as demonstrated by serum creatinine value of * 1.5 × the upper limit of normal (ULN) and either an estimated creatinine clearance value of * 50 mL/min as determined by the Cockcroft-Gault formula or a creatinine clearance value of * 50 mL/min/1.73 m2 based on a 24-hour urine collections. - Subject has adequate liver function as demonstrated by serum bilirubin * 1.5 × ULN and AST and ALT * 2.5 x ULN. For subjects with liver metastasis, AST and ALT < 5 × the ULN. - PTT must be * 1.5 x ULN and INR < 1.5. Subjects on anticoagulant (such as Coumadin) are allowed on study and will have PTT and INR as determined by the Investigator. * Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of the study participation, and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and a negative urine pregnancy test on the first day of study drug administration. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Expanded Safety Cohort #1: Subjects with BRCA1 or BRCA2 Mutated Advanced Solid Tumor * Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Subjects must also have a documented deleterious BRCA1 or BRCA2 mutation. * Subject must have at least 1 site accessible for acquisition of tumor or cell tissue via percutaneous needle, punch, or excisional biopsy to be eligible for enrollment (e.g., cutaneous or subcutaneous, palpable lymph nodes or lesions safely accessible for biopsy). * Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST version 1.1. Expanded Safety Cohort #2: Advanced ovarian cancer, with known germ line mutation of BRCA1 or BRCA2 or no mutation in BRCA1 or BRCA2. . * Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Subjects must also have a known status that is either positive or negative for a documented deleterious BRCA1 or BRCA2 mutation * Subjects with ovarian cancer and non-measurable disease with an elevation of serum CA-125 level by Gynecologic Cancer Intergroup (GCIG) criteria (baseline sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment) may also be in
Exclusion criteria
Exclusion criteria: * Expanded cohort only: Subject has previously received a PARP inhibitor. * Subject has received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within a period of 28 days or 5 half lives (whichever is shorter) prior to Study Day 1. * Subject has known CNS metastases. * Subject has unresolved toxicities from prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE v 4.0) grade 2 or higher clinically significant toxicity (excluding alopecia). * Subject has had major surgery within 28 days prior to Study Day 1. * Clinically significant uncontrolled condition(s) or any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities. * Psychiatric illness/social situation that would limit compliance with study requirements. * Lactating or pregnant female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: Summaries and analyses will be performed with subjects classified by dose level. Exploratory efficacy analyses will be performed on the data collected from the expanded safety cohort portion of the study. Pharmacokinetic: Blood samples for pharmacokinetics of ABT-767 will be collected at designated timepoints throughout the study. Pharmacodynamic: PBMCs will be assayed for PAR levels to evaluate PARP inhibition and exploratory analysis will be performed to correlate with PK and clinical outcomes Safety: Adverse events, laboratory profiles, physical exams, ECGs, and vital signs will be assessed throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Not applicable. | — |
Countries
Netherlands
Outcome results
None listed