Safety/Tolerability Study of AV-412 in Subjects With Refractory or Relapsed Solid Tumor Malignancies
AV-412 is a new oral therapy developed to inhibit the growth of solid tumors in patients who have not responded to standard therapy or surgical interventions, or who have experienced relapse. This study will test the safety of AV-412 and determine the maximum tolerated dose for the treatment of solid tumors.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Daily Oral Administration of AV-412 in Patients With Refractory or Relapsed Solid Tumor Malignancies|
- To evaluate the safety, tolerability, and dose-limiting toxicities (DLT), and determine the maximum tolerated dose (MTD) of AV-412 when administered once daily by the oral route for 4 weeks (4 weeks equals one dosing cycle) [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetic (PK) profile of AV-412 in all patients. Extensive PK collection and assay to be performed in expanded MTD Cohorts [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
- Evaluate potential pharmacodynamic (PD) markers of AV-412 action, in expanded MTD Cohorts ONLY [ Time Frame: two years ] [ Designated as safety issue: No ]
- Preliminary evaluation of the antineoplastic activity of AV-412 (assessed by evidence and duration of disease stabilization or objective response, and time to disease progression) [ Time Frame: two years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2006|
|Study Completion Date:||February 2010|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Daily oral administration of AV-412
Solid oral dosage; 4 dosage strengths; 25, 50, 100, or 200 mg per capsule Dosing Frequency: Once daily dosing for 4 weeks (4 weeks equals 1 cycle)
Although progress has been made, patients with malignancies often either progress after the traditional approach of chemotherapy, surgery, or radiotherapy, or are not candidates for these approaches because of the advances stage of disease. Novel therapies that may offer greater potential than those currently available are urgently needed.
AV 412 is a potent inhibitor of human epidermal growth factor family receptor tyrosine kinases (TKIs) and represents a growing class of anti-cancer agents. The recent introduction of TKIs has opened the door to new approaches to cancer treatment in which the goals of therapy are to halt disease progression, ameliorate symptoms, and improve patient quality of life. AV412 may inhibit growth of solid tumors, with fewer and less debilitating side effects.
This study is designed to determine the safety, tolerability and maximum tolerated dose of daily oral administration of AV 412. Patients will be assigned to escalating drug dose cohorts to determine the optimal dose. Evaluations to determine tolerability include PK, PD, and the adverse events which occur during the course of study drug administration.
|United States, Maryland|
|Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21205|
|Hospital Universitatrio Austral|
|Buenos Aires, Argentina|
|Instituto Médico Especializado Alexander Fleming|
|Buenos Aires, Argentina|
|Principal Investigator:||Manuel Hidalgo, MD, PhD||Johns Hopkins University|
|Principal Investigator:||Justina L Martinez, MD||Hospital Universitatrio Austral|
|Principal Investigator:||Carmen S. Puparelli, MD||Instituto Médico Especializado Alexander Fleming|
|Principal Investigator:||Belén R. Viquiera, M.D.||Centro Integral Oncológica Clara Campal|