The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT05865535
Recruitment Status : Recruiting
First Posted : May 19, 2023
Last Update Posted : April 5, 2024
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Cachexia Biological: AV-380 Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 13, 2023
Estimated Primary Completion Date : July 1, 2025
Estimated Study Completion Date : September 30, 2025
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Cohort 1
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.
 Biological: AV-380
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.
Experimental: Cohort 2
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.
 Biological: AV-380
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.
Experimental: Cohort 3
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.
 Biological: AV-380
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.
Experimental: Cohort 4
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.
 Biological: AV-380
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.
Experimental: Cohort 5
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.
 Biological: AV-380
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Assessment of adverse events (AEs) [ Time Frame: Through 90 days post last dose ]
    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)

  2. Cmax [ Time Frame: Up to 4 months ]
    Maximum Observed Plasma Concentration for AV-380

  3. Serum level of GDF-15 [ Time Frame: Through 90 days post last dose ]
  4. Tmax [ Time Frame: Up to 4 months ]
    Time to Reach the Cmax for AV-380

  5. AUC(0-t) [ Time Frame: Up to 4 months ]
    Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for AV-380


Secondary Outcome Measures :
  1. Weight and body mass index (BMI) [ Time Frame: Through 90 days post last dose ]
  2. Immunogenicity [ Time Frame: Up to 4 months ]
    Serum levels of Anti-Drug Antibody (ADA) against AV-380

  3. 6-minute walk test [ Time Frame: Through 60 days post last dose ]
    Assess aerobic capacity and endurance by measuring the distance covered over a time of 6 minutes

  4. Metabolic Vulnerability Index (MVX) [ Time Frame: Through 60 days post last dose ]
    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.

  5. Handgrip test [ Time Frame: Through 60 days post last dose ]
    Handgrip strength test to measure the maximum isometric strength of the hand and forearm muscles

  6. L3 Skeletal Muscle Index (L3SMI) [ Time Frame: Through 60 days post last dose ]
    Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan

  7. Lean body mass (LBM) [ Time Frame: Through 60 days post last dose ]
    The difference between total body mass and fat mass


Other Outcome Measures:
  1. Best objective response (BOR) [ Time Frame: Through 90 days post last dose ]
    defined as the proportion of patients who have a complete response (CR) or partial response (PR) as determined by the Investigator

  2. Biomarkers [ Time Frame: Through 60 days post last dose ]
    including activin and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1])


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Patient must be ≥ 18 years of age at the time of signing the informed consent.

  2. 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:

    1. CRC patients who are receiving FOLFOX/FOLFOXIRI ± bevacizumab
    2. Pancreatic cancer patients who are receiving FOLFOX/FOLFIRINOX

  3. Patients with cachexia as defined by Fearon criteria:

    1. Weight loss > 5% over past 6 months (in absence of simple starvation), or
    2. BMI < 20 kg/m2 and any degree of weight loss > 2%, or
    3. Sarcopenia and any degree of weight loss > 2%
  4. Patients with life expectancy ≥ 3 months

Exclusion Criteria:

  1. Significant clinical manifestation of any allergic, dermatological, hepatic, renal, hematological, pulmonary, metabolic, cardiovascular, gastrointestinal, neurological, or psychiatric disorders (e.g., anorexia nervosa).
  2. 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.
  3. Significant cardiovascular disease, including myocardial infarction within 3 months prior to start of protocol therapy.
  4. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within the Screening period prior to the first dose of study treatment.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT05865535


Contacts
Layout table for location contacts
Contact: AVEO Clinical Trials Office (857)400-0101 clinical@aveooncology.com

Locations
Layout table for location information
United States, Florida
Advent Health Orlando Hospital Recruiting
Orlando, Florida, United States, 32804
Contact: Corina Mattix    407-303-1327    Corina.mattix@adventhealth.com   
Contact: Iman Boudlal       iman.boudlal@adventhealth.com   
United States, Georgia
Piedmont Cancer Institute Recruiting
Atlanta, Georgia, United States, 30318
Contact: Taiwo Obembe    404-835-6799    TObembe@piedmontcancerinstitute.com   
Contact: Summer Zamadie       SZamadie@piedmontcancerinstitute.com   
Piedmont Cancer Institute Recruiting
Atlanta, Georgia, United States, 30328
Contact: Taiwo Obembe    404-835-6799    TObembe@piedmontcancerinstitute.com   
Contact: Summer Zamdie       SZamadie@piedmontcancerinstitute.com   
Piedmont Cancer Institute Recruiting
Fayetteville, Georgia, United States, 30214
Contact: Taiwo Obembe    404-835-6799    TObembe@piedmontcancerinstitute.com   
Contact: Summer Zamadie       SZamadie@piedmontcancerinstitute.com   
Piedmont Cancer Institute Recruiting
Newnan, Georgia, United States, 30265
Contact: Taiwo Obembe    404-835-6799    TObembe@piedmontcancerinstitute.com   
Contact: Summer Zamadie       SZamadie@piedmontcancerinstitute.com   
Piedmont Cancer Institute Recruiting
Stockbridge, Georgia, United States, 30281
Contact: Taiwo Obembe    404-835-6799    TObembe@piedmontcancerinstitute.com   
Contact: Summer Zamadie       SZamadie@piedmontcancerinstitute.com   
United States, New York
New York Cancer And Blood Specialists Recruiting
Babylon, New York, United States, 17702
Contact: Jessica Nemeth    631-648-2321    jnemeth@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
North Shore Hematology Oncology Associates P.C. dba NY Cancer and Blood Specialists Recruiting
Bronx, New York, United States, 10469
Contact: Sujey Diaz    971-732-4073    sudiaz@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
New York Cancer and Blood Specialists Recruiting
New York, New York, United States, 10028
Contact: Carissa Pederson    917-258-7633    cpedersen@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
New York Cancer And Blood Specialists Recruiting
Patchogue, New York, United States, 11772
Contact: Jessica Nemeth    631-648-2321    jnemeth@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
New York Cancer and Blood Specialists Recruiting
Port Jefferson Station, New York, United States, 11776
Contact: Jessica Nemeth    631-648-2321    jnemeth@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
New York Cancer And Blood Specialists Recruiting
Riverhead, New York, United States, 11901
Contact: Jessica Nemeth    631-648-2321    jnemeth@nycancer.com   
Contact: Megan Stahl       mstahl@nycancer.com   
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Emily Michelich    216-286-3357    Emily.Michelich@UHhospitals.org   
Contact: Megan Boland       Megan.Boland@UHhospitals.org   
United States, South Carolina
MUSC Hollings Cancer Center Recruiting
Charleston, South Carolina, United States, 29425
Contact: Carly Fecio    843-792-3479    fecio@musc.edu   
Contact: Bria Sanders       sandebri@musc.edu   
United States, Washington
Medical Oncology Associates Recruiting
Spokane Valley, Washington, United States, 99216
Contact: Ashley Andrews    509-462-2273    Ashley.Connors@aoncology.com   
Contact: Sophie Miller       Sophie.Miller@aoncology.com   
Medical Oncology Associates Recruiting
Spokane, Washington, United States, 99208
Contact: Ashley Andrews    509-462-2273    Ashley.Connors@aoncology.com   
Contact: Sophie Miller       Sophie.Miller@aoncology.com   
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05865535    
Other Study ID Numbers: AV-380-22-102
First Posted: May 19, 2023    Key Record Dates
Last Update Posted: April 5, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Wasting Syndrome
Cachexia
Neoplastic Processes
Neoplasms
Pathologic Processes
 Weight Loss
Body Weight Changes
Body Weight
Thinness
Metabolic Diseases
Nutrition Disorders