A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02561234
Recruitment Status : Recruiting
First Posted : September 28, 2015
Last Update Posted : April 27, 2018
Information provided by (Responsible Party):
Aeglea Biotherapeutics

Brief Summary:
This is the first-in-human study of the safety of increasing dose levels of AEB1102 in patients with advanced cancers. The study will also evaluate the amounts of AEB1102 in blood, the effects of AEB1102 on blood amino acid levels and tumor growth.

Condition or disease Intervention/treatment Phase
Advanced Cancers Drug: Co-ArgI-PEG Phase 1

Detailed Description:

In this phase I multiple dose, dose escalation study utilizing a classic 3+3 design. Sequential cohorts of patients will receive AEB1102 IV weekly at one of a series of increasing dose levels. Dose escalation will be dependent on the frequency of specific dose-limiting toxicities in the prior cohort of patients. The study will determine the maximum tolerated dose (MTD) of AEB1102, evaluate the safety profile of the compound, assess the pharmacokinetic profile of AEB1102, determine the effect of AEB1102 on blood arginine levels and evaluate the anti-tumor activity of AEB1102.

Following the determination of the MTD, additional cohorts of patients with uveal, cutaneous melanoma and small cell lung cancer will be enrolled and treated with AEB1102 at the MTD.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors
Study Start Date : October 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018

Arm Intervention/treatment
Experimental: AEB1102
AEB1102 (Co-ArgI-PEG) will be administered IV weekly.
Drug: Co-ArgI-PEG
modified human arginase I
Other Name: AEB1102

Primary Outcome Measures :
  1. maximum tolerated dose [ Time Frame: 4 weeks ]
    the dose level at which no more than 1/6 patients experiences dose-limiting toxicity

Secondary Outcome Measures :
  1. safety profile (changes in physical exam, laboratory measures, reported adverse events) [ Time Frame: 4 weeks + ]
    changes in physical exam, laboratory measures, reported adverse events

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

For patients participating in any part of the trial:

  • has an advanced solid tumor previously treated with, or inability to tolerate, standard therapy for the disease, or for which a standard therapy does not exist, and as such is considered a candidate for Phase 1 treatment
  • has adequate organ function: Hgb ≥9 g/dL; absolute neutrophil count (ANC) ≥ 1.5x109/L; plt ≥ 100,000/μL; AST and ALT < 2.5x ULN (< 5x ULN in patients with liver metastases); total bilirubin < 2.0 mg/dL; serum creatinine ≤ 1.5x ULN
  • ECOG performance score 0-2

For patients participating in any expansion group:

  • has measurable disease based on RECIST 1.1 as determined by the treating investigator. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • willing to consent for biopsy is strongly recommended but not mandatory
  • recovery of toxicities related to any prior treatments to at least Grade 1 by CTCAE v 4.03. Exceptions are patients with adverse event(s) that are clinically nonsignificant and/or stable on supportive therapy.

For patients participating in specific expansion groups:

Cutaneous Melanoma:

  • unresectable, locally advanced or metastatic (AJCC stage IIIB, IIIC, or IV) cutaneous malignant melanoma
  • relapsed or progressive disease after or unable to tolerate at least one prior systemic anticancer regimen for metastatic disease involving immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4)
  • in tumors with a relevant BRAF mutation, relapsed, refactory, or unable to tolerate at least one prior systemic anticancer regimen for metastic disease involving a BRAF inhibitor

Uveal Melanoma:

  • uveal melanoma at metastic stage

Small Cell Lung Cancer:

  • extensive disease previously treated with, or inability to tolerate, platinum-based chemotherapy

Exclusion Criteria:

  • has primary CNS malignancy
  • history of untreated brain mets or leptomeningeal disease or spinal cord compression
  • effects of prior anticancer therapy recovered to grade < 2
  • known HIV
  • active infection
  • major surgery within 2 weeks
  • history of another malignancy within 2 years prior

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02561234

Contact: Aeglea Clinical Department 1.855.509.9921

United States, Arizona
Pinnacle Research Recruiting
Phoenix, Arizona, United States, 85258
Contact: Stephanie Althoff         
Principal Investigator: Michael Gordon, MD         
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90024
Contact: Jean Kim         
Principal Investigator: Bart Chmielowski, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Ruth Winslow         
Principal Investigator: Karl Lewis, MD         
United States, Florida
Research Center: Mid Florida Hematology/Oncology Centers Recruiting
Orange City, Florida, United States, 32763
Contact: Santos Nair, MD         
Principal Investigator: Santos Nair, MD         
United States, Massachusetts
Dana Farber Recruiting
Boston, Massachusetts, United States, 02114
Contact: Meagen St. Louis         
Principal Investigator: Elizabeth Buchbinder, MD         
Massachusetts General Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ryan Sullivan, MD         
Principal Investigator: Ryan Sullivan, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 93110
Contact: Siddartha Devarakonda, MD         
Principal Investigator: Siddartha Devarakonda, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Lauren Taiclet         
Principal Investigator: Richard Carvajal, MD         
United States, Oregon
Providence Cancer Center Recruiting
Portland, Oregon, United States, 97213
Contact: Brendan Curti, MD         
Principal Investigator: Brendan Curti, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Richard Shook         
Principal Investigator: Diwakar Davar, MD         
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75230
Contact: James Strauss, MD         
Principal Investigator: James Strauss, MD         
UTSW Recruiting
Dallas, Texas, United States, 75390-8852
Contact: Jessica Williams         
Principal Investigator: David Gerber, MD         
Sponsors and Collaborators
Aeglea Biotherapeutics
Study Director: Jim Joffrion Aeglea Biotherapeutics, Inc.

Responsible Party: Aeglea Biotherapeutics Identifier: NCT02561234     History of Changes
Other Study ID Numbers: CAEB1102-100B
First Posted: September 28, 2015    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018