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

Advanced Cancers Clinical Trial

Official title:

A Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02561234
• Other study ID #: CAEB1102-100B
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2015
• Est. completion date: May 2019

Study information

• Verified date: November 2021
• Source: Aeglea Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancers

Intervention

Drug:
• Co-ArgI-PEG
Administered IV

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber	Boston	Massachusetts
United States	Massachusetts General	Boston	Massachusetts
United States	UTSW	Dallas	Texas
United States	UCLA	Los Angeles	California
United States	Columbia University	New York	New York
United States	Research Center: Mid Florida Hematology/Oncology Centers	Orange City	Florida
United States	Pinnacle Research	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Providence Cancer Center	Portland	Oregon
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Aeglea Biotherapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose	the dose level at which no more than 1/6 patients experiences dose-limiting toxicity	4 weeks
Secondary	safety profile (changes in physical exam, laboratory measures, reported adverse events)	changes in physical exam, laboratory measures, reported adverse events	4 weeks +