The primary objective of this study is to assess the safety, tolerability, and pharmacokinetics of ABT-767 and the effect of food on ABT-767 bioavailability in subjects with BRCA1 or BRCA2 germ line mutation and associated solid tumors (e.g. breast…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
Not applicable.
Background summary
Animal studies have shown that ABT-767 increases the sensitivity of tumor cells
so that chemotherapeutic agents are more effective in killing cancer cells and
causes tumors to shrink, particularly in tumors with the BRCA1 or BRCA2
mutation. ABT-767 is a PARP inhibitor (blocker). PARP is a naturally occurring
protein made by your body that may help cancer cells overcome injury or damage
caused by radiation and certain types of anti-cancer drugs, making these
treatments less effective. ABT-767 inhibits (blocks) the activity of PARP
which may prevent the cancer cell from repairing itself.
Study objective
The primary objective of this study is to assess the safety, tolerability, and
pharmacokinetics of ABT-767 and the effect of food on ABT-767 bioavailability
in subjects with BRCA1 or BRCA2 germ line mutation and associated solid tumors
(e.g. breast, ovarian, prostate, or pancreatic) and in subjects with high grade
serous ovarian, primary peritoneal and fallopian tube cancer.
Study design
Phase 1, open-label, dose escalating study
Intervention
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-767. Dependent on the pharmacokinetic
samples the patient will receive ABT-767 as a once daily dose or a twice-daily
dose.The daily dose given to a patient depends on de cohort the patient is in
and can therefore differ between patients.
In the extended safety cohort 30 patients will receive the RPTD daily.
Study burden and risks
This is the first clinical study of ABT-767 in humans and no information about
adverse events in humans is available. Based on preclinical data possible risk
include: fewer circulating blood cells, decreased number of sperm cells,
decreased bone density, changes of the thymus gland, and damage to the lining
of the intestinal tract. It is not known to what extent these may occur in
humans. Side effects may range from mild to life-threatening.
During screening, C1D-4, C1D1 and C1D8 and ECG will be made. At screening and
in the beginning of every odd cylce, with the exception of cycle 1, a
radiographic tumor assessment will be performed.
The duration of this phase 1 study is not a fixed time point and therefor it is
difficult to esstimate how often the patients will visit the hospital.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
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 included.
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020795-37-NL |
| CCMO | NL33609.078.10 |