Clinical trial NCT00730470: Phase I Study of U3P1287/01, Including Patients With Advanced Solid Tumors
Official title: A Phase I, Open-label, Dose-Finding Study to Assess the Safety and Tolerability of U3-1287 (AMG 888), a Human Monoclonal Antibody Targeting HER3 in Patients With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Human Epidermal Growth Factor Receptor 3
HER3
Heregulin
erb B3
Solid Tumors
Phase I Clinical Study
Lead sponsor: U3 Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2008-08-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 clinical study to investigate the safety, pharmacokinetics, and pharmacodynamics of U3-1287 (AMG 888), a fully human monoclonal antibody targeting the HER3 receptor, in patients with advanced solid tumors. Eligible patients will have disease that is refractory or resistant to standard treatments or for which no standard therapy exists. The study will be conducted in two parts; a dose escalation (Part 1) and a dose expansion (Part 2). The hypothesis for this study is that U3-1287 (AMG888) will be safe and well tolerated in patients with advanced solid tumors and will show initial evidence of anti-tumor activity.


Eligibility criteria: Key Inclusion Criteria:

* Pathologically or cytologically documented advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available, or the patient refuses standard therapy.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Men or women at least 18 years of age
* Adequate hematologic, cardiac, renal, hepatic, metabolic, and coagulation function

Key Exclusion Criteria:

* Presence of untreated or symptomatic brain metastasis.
* Presence of ascites or pleural effusion requiring chronic medical intervention.
* Uncontrolled hypertension
* Concurrent or previous (within 1 week of study day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) or low dose,low molecular weight heparin for prophylaxis against central venous catheter thrombosis.
* Recent major surgical procedure or not yet recovered from major surgery
* Recent participation in clinical drug trials.
* Participation in other investigational procedures.
* Unresolved toxicities from prior anti-cancer therapy
* Patient who is pregnant (e.g. positive human choriogonadotropin \[HCG\] test) or nursing.

Primary outcomes:
measure: To evaluate the safety and tolerability of U3-1287 (AMG888) in patients with advanced solid tumors
timeFrame: Lenth of study
measure: To evaluate maximum tolerated dose (MTD) of U3-1287(AMG888) when administered intravenously to patients with advanced solid tumors
timeFrame: Lenth of study
Secondary outcomes:
measure: Pharmacokinetic Parameters
timeFrame: Length of study
measure: Pharmacodynamic Parameters
timeFrame: Length of study
measure: Human anti-human antibody profile for U3-1287(AMG888)
timeFrame: Length of study
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Centre
state: New York
city: Nashville
country: United States
facility: Vanderbilt Ingram cancer Centre
state: Tennessee
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
Study officials:
References:
citation: LoRusso P, Janne PA, Oliveira M, Rizvi N, Malburg L, Keedy V, Yee L, Copigneaux C, Hettmann T, Wu CY, Ang A, Halim AB, Beckman RA, Beaupre D, Berlin J. Phase I study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2013 Jun 1;19(11):3078-87. doi: 10.1158/1078-0432.CCR-12-3051. Epub 2013 Apr 16.