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A Dose Escalation Study of AV-380 in Metastatic Cancer Patients With Cachexia

Primary Purpose

Cachexia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AV-380
Sponsored by
AVEO Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cachexia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient must be ≥ 18 years of age at the time of signing the informed consent. Patients with histologically confirmed metastatic CRC or pancreatic cancer, who are actively receiving SoC chemotherapy in the first line setting for metastatic disease; eligible patients must have completed at least 2 Cycles of chemotherapy to eligible: CRC patients who are receiving FOLFOX/FOLFOXIRI ± bevacizumab Pancreatic cancer patients who are receiving FOLFOX/FOLFIRINOX Patients with cachexia as defined by Fearon criteria: Weight loss > 5% over past 6 months (in absence of simple starvation), or BMI < 20 kg/m2 and any degree of weight loss > 2%, or Sarcopenia and any degree of weight loss > 2% Patients with life expectancy ≥ 3 months Exclusion Criteria: Significant clinical manifestation of any allergic, dermatological, hepatic, renal, hematological, pulmonary, metabolic, cardiovascular, gastrointestinal, neurological, or psychiatric disorders (e.g., anorexia nervosa). Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before first dose of study treatment. Significant cardiovascular disease, including myocardial infarction within 3 months prior to start of protocol therapy. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within the Screening period prior to the first dose of study treatment.

Sites / Locations

  • Piedmont Cancer InstituteRecruiting
  • New York Cancer and Blood SpecialistsRecruiting
  • New York Cancer and Blood SpecialistsRecruiting
  • New York Cancer and Blood SpecialistsRecruiting
  • University Hospitals Cleveland Medical CenterRecruiting
  • Summit Cancer CentersRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Arm Description

IV infusion of AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.

IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.

IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.

IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.

IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.

Outcomes

Primary Outcome Measures

Assessment of adverse events (AEs)
AEs as characterized by incidence, type, frequency, and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
Cmax
Maximum Observed Plasma Concentration for AV-380
Serum level of GDF-15
Tmax
Time to Reach the Cmax for AV-380
AUC(0-t)
Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for AV-380

Secondary Outcome Measures

Weight and body mass index (BMI)
Immunogenicity
Serum levels of Anti-Drug Antibody (ADA) against AV-380
6-minute walk test
Assess aerobic capacity and endurance by measuring the distance covered over a time of 6 minutes
Metabolic Vulnerability Index (MVX)
The MVX is a blood test that combines results from analytes that represent metabolic malnutrition (MMX; valine, leucine, isoleucine, citrate) and inflammation (IFX; GlycA and S-HDLP) to provide a single prognostic score (1-100) for risk of death.
Handgrip test
Handgrip strength test to measure the maximum isometric strength of the hand and forearm muscles
L3 Skeletal Muscle Index (L3SMI)
Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan
Lean body mass (LBM)
The difference between total body mass and fat mass

Full Information

First Posted
May 2, 2023
Last Updated
August 24, 2023
Sponsor
AVEO Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05865535
Brief Title
A Dose Escalation Study of AV-380 in Metastatic Cancer Patients With Cachexia
Official Title
A Phase 1 Dose Escalation Study of AV-380 in Combination With Standard of Care Chemotherapy in Metastatic Cancer Patients With Cachexia and Elevated GDF-15 Levels
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 13, 2023 (Actual)
Primary Completion Date
November 18, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AVEO Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in metastatic cancer patients with Cachexia. AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cachexia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
IV infusion of AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.
Intervention Type
Biological
Intervention Name(s)
AV-380
Intervention Description
AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.
Primary Outcome Measure Information:
Title
Assessment of adverse events (AEs)
Description
AEs as characterized by incidence, type, frequency, and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
Time Frame
Through 90 days post last dose
Title
Cmax
Description
Maximum Observed Plasma Concentration for AV-380
Time Frame
Up to 4 months
Title
Serum level of GDF-15
Time Frame
Through 90 days post last dose
Title
Tmax
Description
Time to Reach the Cmax for AV-380
Time Frame
Up to 4 months
Title
AUC(0-t)
Description
Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for AV-380
Time Frame
Up to 4 months
Secondary Outcome Measure Information:
Title
Weight and body mass index (BMI)
Time Frame
Through 90 days post last dose
Title
Immunogenicity
Description
Serum levels of Anti-Drug Antibody (ADA) against AV-380
Time Frame
Up to 4 months
Title
6-minute walk test
Description
Assess aerobic capacity and endurance by measuring the distance covered over a time of 6 minutes
Time Frame
Through 60 days post last dose
Title
Metabolic Vulnerability Index (MVX)
Description
The MVX is a blood test that combines results from analytes that represent metabolic malnutrition (MMX; valine, leucine, isoleucine, citrate) and inflammation (IFX; GlycA and S-HDLP) to provide a single prognostic score (1-100) for risk of death.
Time Frame
Through 60 days post last dose
Title
Handgrip test
Description
Handgrip strength test to measure the maximum isometric strength of the hand and forearm muscles
Time Frame
Through 60 days post last dose
Title
L3 Skeletal Muscle Index (L3SMI)
Description
Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan
Time Frame
Through 60 days post last dose
Title
Lean body mass (LBM)
Description
The difference between total body mass and fat mass
Time Frame
Through 60 days post last dose
Other Pre-specified Outcome Measures:
Title
Best objective response (BOR)
Description
defined as the proportion of patients who have a complete response (CR) or partial response (PR) as determined by the Investigator
Time Frame
Through 90 days post last dose
Title
Biomarkers
Description
including activin and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1])
Time Frame
Through 60 days post last dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must be ≥ 18 years of age at the time of signing the informed consent. Patients with histologically confirmed metastatic CRC or pancreatic cancer, who are actively receiving SoC chemotherapy in the first line setting for metastatic disease; eligible patients must have completed at least 2 Cycles of chemotherapy to eligible: CRC patients who are receiving FOLFOX/FOLFOXIRI ± bevacizumab Pancreatic cancer patients who are receiving FOLFOX/FOLFIRINOX Patients with cachexia as defined by Fearon criteria: Weight loss > 5% over past 6 months (in absence of simple starvation), or BMI < 20 kg/m2 and any degree of weight loss > 2%, or Sarcopenia and any degree of weight loss > 2% Patients with life expectancy ≥ 3 months Exclusion Criteria: Significant clinical manifestation of any allergic, dermatological, hepatic, renal, hematological, pulmonary, metabolic, cardiovascular, gastrointestinal, neurological, or psychiatric disorders (e.g., anorexia nervosa). Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before first dose of study treatment. Significant cardiovascular disease, including myocardial infarction within 3 months prior to start of protocol therapy. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within the Screening period prior to the first dose of study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AVEO Clinical Trials Office
Phone
(857)400-0101
Email
clinical@aveooncology.com
Facility Information:
Facility Name
Piedmont Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Individual Site Status
Recruiting
Facility Name
New York Cancer and Blood Specialists
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Individual Site Status
Recruiting
Facility Name
New York Cancer and Blood Specialists
City
New York
State/Province
New York
ZIP/Postal Code
10028
Country
United States
Individual Site Status
Recruiting
Facility Name
New York Cancer and Blood Specialists
City
Port Jefferson Station
State/Province
New York
ZIP/Postal Code
11776
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
Summit Cancer Centers
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Dose Escalation Study of AV-380 in Metastatic Cancer Patients With Cachexia

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