First-in-human Study of AB0024 to Evaluate Safety and Tolerability in Adults With Advanced Solid Tumors

Tracking Information
First Submitted Date ICMJE	March 24, 2011
First Posted Date ICMJE	March 28, 2011
Last Update Posted Date	May 3, 2012
Study Start Date ICMJE	June 2010
Actual Primary Completion Date	March 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 24, 2011)	To characterize the safety, tolerability, and pharmacokinetics (PK) of AB0024 after multiple intravenous (IV) administrations in patients with advanced solid tumors. [ Time Frame: Day 71 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01323933 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 24, 2011)	To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors (RECIST) and to evaluate the formation of anti-AB0024 antibodies. [ Time Frame: Day 71 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	First-in-human Study of AB0024 to Evaluate Safety and Tolerability in Adults With Advanced Solid Tumors
Official Title ICMJE	A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AB0024 in Adult Patients With Advanced Solid Tumors
Brief Summary	Analysis of safety, tolerability, and PK data will provide information that will guide future development of AB0024.
Detailed Description	This is a first-in-human, open-label, sequential dose escalation study to evaluate AB0024 in patients with advanced solid tumors. The study will consist of two parts: Part A will be a dose escalation, and Part B will be a dose expansion.The primary objective of this study is to characterize the safety, tolerability, and PK of AB0024 after multiple IV administrations in patients with advanced solid tumors. The secondary objectives are to measure the tumor response by modified RECIST and to evaluate the formation of anti-AB0024 antibodies. Patients will receive infusions of AB0024 every two weeks. Patients will be seen weekly for safety assessments and collection of blood samples. Patients who do not show evidence of disease progression by clinical assessment or by CT or MRI may continue receiving AB0024 every 2 weeks until disease progression (clinical or radiographic), study drug intolerance, or withdrawal of consent.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Neoplasms
Intervention ICMJE	Drug: AB0024; Comparison of different dosages of drug
Study Arms	Experimental: AB0024; The starting dose for Part A will be 1 mg/kg. Subsequent doses of 3, 10, and 20 mg/kg are planned. Three to 6 patients will be enrolled using a 3 + 3 design. Doses of AB0024 will be administered on Days 1, 15, 29, and 43 to characterize the safety, tolerability, and PK. The dose expansion phase of the study will begin upon completion of the dose escalation phase. Up to 20 patients will be enrolled into one or two cohorts of Part B. The first expansion cohort will be dosed up to the MTD defined as the highest dose level with an observed incidence of DLT in <33% of patients enrolled from Part A.; Intervention: Drug: AB0024
Publications *	Barker HE, Cox TR, Erler JT. The rationale for targeting the LOX family in cancer. Nat Rev Cancer. 2012 Jul 19;12(8):540-52. doi: 10.1038/nrc3319. Review.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 2, 2012)	32
Original Estimated Enrollment ICMJE; (submitted: March 24, 2011)	44
Actual Study Completion Date	March 2012
Actual Primary Completion Date	March 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to, intolerant of, or for which no standard of therapy is available; Measurable or evaluable disease; ECOG Performance Status of ≤2; No known active central nervous system (CNS) tumors or CNS metastases; Adequate organ function Exclusion Criteria: Myocardial infarction within the last 6 months of study Day 1, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication; History of surgery within 28 days prior to enrollment or anticipated surgery during the study period; Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 28 days of study Day 1 (six weeks for nitrosoureas, mitomycin C, antibodies, or molecular agents with t½ >10 days); (concurrent use of hormone therapy for breast or prostate cancer is permitted); Treatment with immune modulators including, but not limited to, cyclosporine and tacrolimus within two weeks prior to enrollment; Concurrent or prior (within 30 days of study Day 1) anticoagulation therapy; (low-dose warfarin [<2 mg/day] for prophylaxis against central venous catheter thrombosis is allowed); Patient with tumor that is infiltrating or invading a major blood vessel
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01323933
Other Study ID Numbers ICMJE	AB0024-101
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Zung Thai, MD/ Medical Monitor, Gilead Sciences
Study Sponsor ICMJE	Gilead Sciences
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Patricia LoRusso, DO Barbara Ann Karmanos Cancer Institute Principal Investigator: Anthony Tolcher, MD South Texas Accelerated Research Therapeutics
PRS Account	Gilead Sciences
Verification Date	May 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP