An Open-Label, Randomized, Phase 2 Study of Efficacy and Tolerability of ABT-869 in Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

• Conditions: Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC); MedDRA version: 9.1Level: LLTClassification code 10061873Term: Non-small cell lung cancer; MedDRA version: 9.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOS; MedDRA version: 9.1Level: LLTClassification code 10029519Term: Non-small cell lung cancer stage III; MedDRA version: 9.1Level: LLTClassification code 10059515Term: Non-small cell lung cancer metastatic; MedDRA version: 9.1Level: LLTClassification code 10029521Term: Non-small cell lung cancer stage IIIB; MedDRA version: 9.1Level: LLTClassification code 10029515Term: Non-small cell lung cancer recurrent; MedDRA version: 9.1Level: LLTClassification code 10029516Term: Non-small cell lung cancer stage 0; MedDRA version: 9.1Level: LLTClassification code 10029517Term: Non-small cell lung cancer stage I; MedDRA version: 9.1Level: LLTClassification code 10029518Term: Non-small cell lung cancer stage II

• Registration Number: EUCTR2007-005245-37-GB
• Lead Sponsor: Abbott GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-25
• Last Update Posted: 29 July 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Subject must be = 18 years of age.
2. Subject must be histologically or cytologically diagnosed with locally advanced or
metastatic NSCLC.
3. Subjects must have at least one lesion measurable by CT scan as defined by
RECIST. The measurable lesion may have not received radiation therapy.
4. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status
of 0-2.
5. Subject has received at least one prior line of systemic treatment but no more than two treatment regimens for locally advanced or metastatic NSCLC not amenable to cure.
6. Subject must have the following laboratory values:
? Total Bilirubin = 1.5 × upper normal limit (ULN)
? AST/ALT = 2.5 × ULN or = 5.0 ULN if subject has liver metastasis
? PTT = 1.5 × ULN and INR = 1.5
? ANC = 1.0 × 109/L
? Platelet count = 75 × 109/L
? Creatinine = 1.5 × ULN
7. No other active malignancy within the past 5 years except for cervical cancer in
situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
8. Women of childbearing potential and men must agree to use adequate
contraception (one of the following listed below) prior to study entry, for the
duration of study participation and up to two months following completion of
therapy. Women of childbearing potential must have a negative urine pregnancy
test within 7 days prior to initiation of treatment and/or post menopausal women
must be amenorrheic for at least 12 months to be considered of non-childbearing
potential.
? Total abstinence from sexual intercourse (minimum one complete menstrual
cycle)
? A vasectomized partner
? Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
? Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicidal jellies or cream)
Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for two months following completion of therapy.
9. Subject is capable of understanding and complying with parameters as outlined in
the protocol and able to sign and date the informed consent, approved by an
Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to
the initiation of any screening or study-specific procedures.
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

1. Subject has received anti-cancer therapy within 21 days or 5 half lives, whichever
is shorter, prior to study drug administration. Anti-cancer therapies include but are
not limited to: investigational agents, immunotherapy, anti-cancer traditional
Chinese medicine/herbal remedies, hormonal, targeted agents (i.e., erlotinib,
imatinib) or biologic therapy. Subject has received cytotoxic chemotherapy (i.e.,
alkylating agents, microtubule inhibitors, anti-metabolites) within 21 days prior to study drug administration. In addition, subject has not recovered to = Grade 1
clinically significant adverse effects/toxicities of previous therapy.
2. Subject has received radiation or undergone major surgery within the previous
21 days prior to study drug administration.
3. Subject has received targeted VEGF/PDGF TKI (tyrosine kinase inhibitor) therapy
(prior Avastin is allowed).
4. Subject has untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are
radiographically or clinically stable for at least 4 weeks after therapy and have no
evidence of cavitation or hemorrhage in the brain lesion are eligible providing that
they are asymptomatic and do not require corticosteroids (must have discontinued
steroids at least 1 week prior to study drug administration).
5. History of greater than 10% weight loss during the 6 weeks prior to study entry.
6. Subject has significant central thoracic lesions invading or abutting the heart or
major blood vessels with any appreciable cavitation.
7. Subject has clinically relevant hemoptysis described as > 5 ml fresh blood within
the last 3 months. Subjects with only flecks of blood in sputum are permitted.
8. The subject has proteinuria CTC Grade > 1 at baseline as measured by a UPC ratio
of > 1 and confirmed by a 24 hour urine collection.
9. The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 100 mmHg or systolic blood
pressure > 150 mmHg. Subjects may be re-screened if blood pressure is shown to
be controlled with or without intervention.
10. The subject has a documented left ventricular ejection fraction < 50%.
11. Subject is receiving therapeutic anticoagulation therapy. Low dose
anti-coagulation (e.g., low dose Warfarin) for catheter prophylaxis only will be
permitted. No low molecular weight heparin is allowed.
12. Subject is receiving anti-retroviral therapy for HIV.
13. Female subjects who are pregnant or breast-feeding.
14. Clinically significant uncontrolled condition(s) including:
? Active uncontrolled infection
? Class III or IV heart failure as defined by the New York Heart Association
functional classification system
? Unstable angina pectoris or cardiac arrhythmia
? Myocardial infarction within last 6 months
? History of adrenal insufficiency
? History of hemorrhagic cerebral vascular accident within last 6 months
? Active ulcerative colitis, Crohn's disease, celiac disease or any other
conditions that interfere with absorption
? History of autoimmune disease that has kidney involvement
? History of overt bleeding (> 30 mL bleeding/episode) within 3 months of
study drug administration
? Psychiatric illness/social situation that would limit compliance with study
requirements
? Any other medical condition, which in the opinion of the study investigator
places the su

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy of 0.10 mg/kg and 0.25 mg/kg ABT-869 using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and to establish the safety/tolerability profile of ABT-869 in subjects with advanced or metastatic NSCLC.;Secondary Objective: To identify potential biomarkers that correlate and/or predict efficacy and toxicity in subjects with advanced or metastatic NSCLC and to explore if there are any ethnic differences in tumor response to ABT-869 between Asian and non-Asian NSCLC populations. The tertiary objectives of this study are to assess additional efficacy endpoints such as quality of life, changes in weight and performance status.;Primary end point(s): Determine the efficacy of low and high dosages using RECIST and establish safety and tolerability of ABT-869 in NSCLC.