A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects with Small Cell Lung Cancer (SCLC) or other non-hematological malignancies.
- Conditions
- Small cell lung carcinoma (SCLC) (North America or UK) and other non-hematological malignancies (North America only).MedDRA version: 8.1Level: LLTClassification code 10041067Term: Small cell lung cancer
- Registration Number
- EUCTR2006-003298-28-GB
- Lead Sponsor
- Abbott Laboratories Limited (Queenborough, Kent, ME11 5EL, England)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Phase 1:<br>- safety assessment<br>- dose limiting toxicity 9DLT) determination<br>- maximum tolerated dose (MTD) determination<br>- pharmacokinetic profile evaluation<br>Phase 2:<br>- safety assessment at the recommended Phase 2 dose (RPTD)<br>- preliminary efficacy assessment ;Secondary Objective: ;Primary end point(s): As this is Phase 1/2a study, there is no primary endpoint.<br>The objectives of the Phase 1 study include:<br>?Safety assessment<br>?Dose limiting toxicity (DLT) determination<br>?Maximum tolerated dose (MTD) determination<br>?Pharmacokinetic profile evaluation<br><br>The objectives of the Phase 2a study include:<br>?Safety assessment at the recommended Phase 2 dose (RPTD)<br>?Preliminary efficacy assessment<br>
- Secondary Outcome Measures
Name Time Method