| Criteria: |
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Inclusion Criteria:
- ECOG performance score of </= 2
- Subjects who have completed dosing with ABT-263 during a previous study
- For Arm A (ABT-263 and Erlotinib) and Arm B (ABT-263 and Irinotecan), subjects
should have histologically and/or cytologically documented cancer for which
irinotecan or erlotinib has been determined to be an appropriate therapy as
determined by the Investigator
- For Arm C (ABT-263 monotherapy), subject should have a malignancy that is either
relapsed or refractory to standard therapy, or no known effective therapy exists
- Adequate bone marrow, renal and hepatic function per local laboratory reference range
as follows:
- Bone marrow: Absolute Neutrophil count (ANC) >/= 1,000/microL
- Platelets >/= 100,000/mm3 (>/= 150,000/mm3 for irinotecan combination)
independent of platelet transfusions within 3 months prior to starting study
drug)
- Hemoglobin >/= 9.0 g/dL
- Renal function: serum creatinine </= 2.0 mg/dL or calculated creatinine clearance
>/= 50 mL/min
- Hepatic function and enzymes: AST and ALT </= 3.0 x the upper limit of normal (ULN)
of institution's normal range
- Bilirubin </= 1.5 x ULN. Subjects with Gilbert's Syndrome may have a Bilirubin
> 1.5 ULN
- Subjects with liver metastasis may have an AST and ALT of </= 5.0 x the upper limit
of normal
- Coagulation: aPTT, PT not to exceed 1.2 x ULN
- Subjects with neurologic symptoms (e.g., visual problems, headache, seizure) must
have documented brain imaging (MRI or CT) within 28 days prior to the first dose of
study drug. If imaging is performed, then subject should be negative for subdural or
epidural hematoma. Subjects with brain metastases must have clinically controlled
symptoms as 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 first dose of study drug
- Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or
have negative results for a pregnancy test
- Female subjects not surgically sterile or postmenopausal (for at least 1 year) and
non-vasectomized male subjects must practice at least one of the following methods of
birth control: total abstinence, a vasectomized partner, oral contraceptives,
double-barrier method
- Subjects must voluntarily sign and date an informed consent, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the
initiation of any screening or study-specific procedures.
Exclusion Criteria:
- Subject has undergone an allogeneic stem cell transplant
- Has an underlying, predisposing condition of bleeding or currently exhibits signs of
bleeding
- A recent history of non-chemotherapy induce thrombocytopenic associated bleeding
within 1 year prior to the first dose of study drug
- Active peptic ulcer disease or other hemorrhagic esophagitis/gastritis
- A significant history of cardiovascular disease (e.g., MI, thrombotic or
thromboembolic event in the last 6 months), renal, neurologic, psychiatric,
endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the
Investigator would adversely affect his/her participating in this study
- Pregnant or breast-feeding
- Tested positive for HIV (due to potential drug-drug interactions between
anti-retroviral inhibitors and ABT-263, as well as anticipated ABT-263 mechanism
based lymphopenia that may potentially increase the risk of opportunistic infections
and potential drug-drug interactions with certain anti infective agents)
- Exhibits evidence of other clinically significant uncontrolled condition(s)
including, but not limited to: active systemic fungal infection, diagnosis of fever
and neutropenia within 1 week prior to study drug administration; received any of the
following anti-cancer therapy 14 days prior to the first dose of study drug, or has
not recovered to less than Grade 2 clinically significant adverse
effect(s)/toxicity(s) of the previous therapy: chemotherapy, immunotherapy,
radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen
replacement therapy [ERT], or agonists required to suppress serum testosterone levels
[e.g., LHRH, GnRH, etc.] for subjects with prostate cancer if on a stable dose for 21
days prior to the first dose of study drug), any investigational therapy other than
ABT-263, including targeted small molecule agents
- Received a biologic agent for anti-neoplastic intent within 30 days prior to the
first dose of study drug
- currently receiving or requires anticoagulation therapy or any drugs or herbal
supplements that affect platelet function, with the exception of low-dose
anticoagulation medications such as heparin that are used to maintain the patency of
a central venous catheter;
- received aspirin within 7 days prior to the first dose of study drug and during
ABT-263 administration;
- consumed grapefruit or grapefruit products within 3 days prior to the first dose of
study drug, history of hypersensitivity to erlotinib or other polysorbate 80 drugs
(not applicable for ABT-263 monotherapy);
- received ketoconazole 7 days prior to the administration of the first dose of
irinotecan. (Arm B only);
- received ABT-263 within 3 days prior to the first dose of study drug (not applicable
for ABT-263 monotherapy);
- and in the opinion of the Investigator, the subject is an unsuitable candidate to
receive ABT-263. |