A Phase 1 Safety and Pharmacokinetic Study of ABT-263 in Combination With Gemzar® (Gemcitabine) in the Treatment of Subjects With Solid Tumors
- Age greater then or equal to 18 years.
- For the 21 and 28-day dose escalation cohorts and the 21-day safety expansion cohort
subjects must have histologically and/or cytologically documented cancer for which
gemcitabine has been determined to be an appropriate therapy, per the Investigator.
- For the 28-day safety expansion cohort, subjects must have histologically and/or
cytologically documented ductal adenocarcinoma or undifferentiated carcinoma of the
pancreas for which gemcitabine has been determined to be an appropriate first-line
therapy, per the investigator.
Note: If the 28-day dose escalation schedule is deemed intolerable and further dose
de-escalation is not explored, the expanded safety cohort will evaluate navitoclax
(ABT-263) in combination with gemcitabine in an additional 12 to 15 subjects with
histologically ductal adenocarcinoma or undifferentiated carcinoma of the pancreas for
which gemcitabine has been determined to be an appropriate first-line therapy with the
RPTD and schedule from the 21-day portion of the study.
- Measurable disease by CT or MRI as defined RECIST.
- Subjects with brain metastases must have clinically controlled neurologic symptoms,
defined as surgical excision and/or radiation therapy followed by 21 days of stable
neurologic function and no evidence of CNS disease progression as determined by CT or
MRI within 28 days prior to the 1st dose of study drug.
- ECOG less then or equal to 1.
- Must have adequate bone marrow, renal and hepatic function per local laboratory
reference range as follows:
- Bone marrow:Absolute Neutrophil Count greater then or equal to1500/μL; platelets
greater then or equal to 150,000/mm^3; hemoglobin greater then or equal to 9.0
- Renal function: Serum creatinine less then or equal to 2.0 mg/dL or calculated
creatinine clearance greater then or equal to 50 mL/min;
- Hepatic function and enzymes: AST , ALP and ALT less then or equal to 3.0 × the
upper limit of normal (ULN), bilirubin less then or equal to 1.5 × ULN.
- Subjects with liver metastasis may have AST, ALP, and ALT less then or equal to
5.0 X ULN.
- Subjects with bone metastasis may have ALP less then or equal to 5.0 × ULN;
Coagulation: aPTT and PT not to exceed 1.2 × ULN.
- Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or
have negative results for a pregnancy test performed as follows: at Screening via
serum sample obtained within 14 days prior to initial study drug administration and
prior to dosing via urine sample obtained on Cycle 1 Day 1, if it has been greater
then 7 days since obtaining the serum pregnancy test results.
- Female subjects not surgically sterile or postmenopausal (for at least 1 year) and
non-vasectomized male subjects must practice at least 1 of the following methods of
- total abstinence from sexual intercourse (minimum 1 complete menstrual cycle);
- vasectomized partner;
- hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months
prior to study drug administration;
- Double-barrier method (including condoms, contraceptive sponge, diaphragm or
vaginal ring with spermicidal jellies or cream).
- Underlying, predisposing condition of bleeding or currently exhibits signs of
- Recent history of thrombocytopenia associated with bleeding w/i 1 year prior to 1st
dose of study drug.
- Currently receiving or requires anticoagulation therapy or any drugs or herbal
supplements that affect platelet function, w/the exception of low-dose
anticoagulation medications that are used to maintain the patency of a central iv
- Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis.
- Active immune thrombocytopenic purpura, autoimmune hemolytic anemia or a history of
being refractory to platelet transfusions (w/i 1 year prior to the 1st dose of study
- Received radio-immunotherapy w/i 6 months prior to 1st dose of study drug.
- Received an antibody therapy or other biologics (with the exception of colony
stimulating factors [G-CSF,GM-CSF] or erythropoietin) w/i 28 days prior to 1st dose
of study drug.
- Received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy,
hormonal therapy (with the exception of hormones for hypothyroidism, ERT,
anti-estrogen analogs, LHRH, GnRH agonists required to suppress serum testosterone
levels if on a stable dose for at least 21 days prior to the 1st dose of study
drug), or any investigational therapy w/i 14 days prior to the 1st dose of study
drug, or has not recovered to less than a grade 2 clinically significant adverse
effect(s)/ toxicity(s) of the previous therapy.
- Received steroid therapy for anti-neoplastic intent w/i 7 days prior to the 1st dose
of study drug. (Inhaled steroids for asthma, topical steroids, replacement/stress
corticosteroids, or corticosteroids taken as premedication for this study will not be
- Received aspirin w/i 7 days prior to 1st dose of study drug.
- History of hypersensitivity to gemcitabine.Positive for HIV.
- Significant history of cardiac, renal, neurologic, psychiatric, endocrinologic,
metabolic, immunologic, or hepatic disease.
- Exhibits evidence of other clinically significant uncontrolled condition; active
systemic fungal infection;diagnosis of fever & neutropenia w/i 1 week prior to study
- The subject has undergone prior procedures or has active gastrointestinal disease
that would result in the inability to adequately absorb an oral medication (e.g.,
uncontrolled nausea, vomiting, inflammatory disease, bowel obstruction, or a major