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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02561234
Recruitment Status : Completed
First Posted : September 28, 2015
Last Update Posted : October 14, 2019
Sponsor:
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 Phase 2

Detailed Description:

In this phase I/2 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors
Study Start Date : October 2015
Actual Primary Completion Date : May 2019
Actual Study Completion Date : May 2019

Arm Intervention/treatment
Experimental: AEB1102 Dose Escalation Cohort 1
3 patients dosed at 0.01 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 2
4 patients dosed at 0.02 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 3
4 patients dosed at 0.04 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 4
4 patients dosed at 0.08 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 5
3 patients dosed at 0.12 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 6
4 patients dosed at 0.18 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 7
5 patients dosed at 0.27 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 8
7 patients dosed at 0.40 mg/kg until MTD determined
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Dose Escalation Cohort 9
7 patients dosed at 0.33 mg/kg until MTD determined MTD determined at 0.33 mg/kg
Drug: Co-ArgI-PEG
Administered IV
Other Name: AEB1102

Experimental: AEB1102 Expansion
Uveal: 11 patients dosed at 0.33 mg/kg Cutaneous Melanoma: 11 dosed at 0.33 mg/kg SCLC: 13 patients dosed at 0.33 mg/kg
Drug: Co-ArgI-PEG
Administered IV
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



Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT02561234


Locations
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United States, Arizona
Pinnacle Research
Phoenix, Arizona, United States, 85258
United States, California
UCLA
Los Angeles, California, United States, 90024
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Research Center: Mid Florida Hematology/Oncology Centers
Orange City, Florida, United States, 32763
United States, Massachusetts
Dana Farber
Boston, Massachusetts, United States, 02114
Massachusetts General
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 93110
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Oregon
Providence Cancer Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
UTSW
Dallas, Texas, United States, 75390-8852
Sponsors and Collaborators
Aeglea Biotherapeutics
Investigators
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Study Director: Jim Joffrion Aeglea Biotherapeutics, Inc.
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Responsible Party: Aeglea Biotherapeutics
ClinicalTrials.gov Identifier: NCT02561234    
Other Study ID Numbers: CAEB1102-100B
First Posted: September 28, 2015    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019