Small cell lung carcinoma (SCLC) (North America or UK) and other non-hematological malignancies (North America only). MedDRA version: 8.1 Level: LLT Classification code 10041067 Term: Small cell lung cancer
Conditions
Interventions
Product Name: ABT-263
Product Code: ABT-263
Pharmaceutical Form: Powder for oral solution
Current Sponsor code: ABT-263
Other descriptive name: A-855071.3
Concentration unit: g gram(s)
Concentration t
Sponsors
Abbott Laboratories Limited (Queenborough, Kent, ME11 5EL, England)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1 1. The subject must be = 18 years of age. 2. The subject must have histologically documented diagnosis of small cell lung cancer (North America and UK) or other non-hematological malignancy (North America only) measurable by CT or MRI as defined by RECIST. Target lesion(s) may not have received radiation therapy. 3. The subject has received at least 1 prior chemotherapy treatment regimen(s) and their disease is refractory or the subject has experienced progressive disease following the treatment. 4. 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 21 days prior to the first dose of study drug. 5. The subject has an Eastern Cooperative Oncology Group performance score of = 2. 6. Subjects receiving Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants (e.g., Prozac) must be receiving a stable dose for at least 21 days prior to the first dose of study drug. 7. Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference range at Screening (see protocol). 8. Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test (see protocol for details of pregancy test) 9. All female subjects not surgically sterile or postmenopausal (for at least one year) and non-vasectomized male subjects must practice suitable method(s) of birth control (as defined in the protocol). 10. The subject, or legal representative, must voluntarily sign and date an informed consent, apprpved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. 11. In the Investigator's opinion, the subject's life expectancy is at least 30 days. Phase 2a: Criteria 1,4,6,7,8,9, 10, 11 for phase 1, plus criteria (numbered as they appear in the protocol): 2. The subject must have histologically documented diagnosis of small cell lung cancer (SCLC). 3. The subject has extensive-stage SCLC and is chemotherapy naïve (US only) or the subject has experienced progressive disease following at least one chemotherapy regimen or their disease is refractory. 5. 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 21 days prior to the first dose of study drug. 12. The subject, or legal representative, 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. 13. In the investigator's opinion, the subject's life expectancy is at least 30 days. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Phases 1 & 2a 1. The subject has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of non-chemotherapy induced thrombocytopenia-associated bleeding within one year prior to first dose of study drug. 2. The subject has active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis. 3. The subject has a history of platelet autoantibodies or autoimmune phenomena including immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA). 4. Subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter. 5. The subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), biologic (with the exception of colony stimulating factors [G-CSF, GM-CSF] or erythropoietin), or any investigational therapy within 14 days prior to the first 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. 6. The subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug. 7. The subject has 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. Questions regarding inclusion of individual subjects should be directed to the Abbott Medical Monitor or designee. 8. A female subject is pregnant or breast-feeding. 9. The subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral medications 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). 10. The subject has previous or current malignancies at other sites, with the exception of: ? adequately treated in situ carcinoma of the cervix uteri; ? basal or squamous cell carcinoma of the skin; ? previous nonpulmonary malignancy (e.g., localized prostate cancer) confined and surgically resected with no evidence of disease within three years. 11. The subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: ? active systemic fungal infection; ? diagnosis of fever and neutropenia within one week prior to study drug administration. 12. Subject has received aspirin within seven days prior to the first dose of study drug. 13. The subject has received steroid therapy within seven days prior to the first dose of study drug with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: - safety assessment - dose limiting toxicity 9DLT) determination - maximum tolerated dose (MTD) determination - pharmacokinetic profile evaluation Phase 2: - safety assessment at the recommended Phase 2 dose (RPTD) - preliminary efficacy assessment ;Secondary Objective: ;Primary end point(s): As this is Phase 1/2a study, there is no primary endpoint. The objectives of the Phase 1 study include: ? Safety assessment ? Dose limiting toxicity (DLT) determination ? Maximum tolerated dose (MTD) determination ? Pharmacokinetic profile evaluation The objectives of the Phase 2a study include: ? Safety assessment at the recommended Phase 2 dose (RPTD) ? Preliminary efficacy assessment | — |
Countries
United Kingdom
Outcome results
None listed