Clinical trial NCT01323933: First-in-human Study of AB0024 to Evaluate Safety and Tolerability in Adults With Advanced Solid Tumors
Official title: A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AB0024 in Adult Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Solid tumors
Oncology
Cancer
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-03-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To characterize the safety, tolerability, and pharmacokinetics (PK) of AB0024 after multiple intravenous (IV) administrations in patients with advanced solid tumors.
timeFrame: Day 71
Secondary outcomes:
measure: To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors (RECIST) and to evaluate the formation of anti-AB0024 antibodies.
timeFrame: Day 71
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Patricia LoRusso, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: South Texas Accelerated Research Therapeutics
name: Anthony Tolcher, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.