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Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (REMD-477)

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ClinicalTrials.gov Identifier: NCT04330625
Recruitment Status : Recruiting
First Posted : April 1, 2020
Last Update Posted : November 20, 2020
Sponsor:
Information provided by (Responsible Party):
Herbert Lyerly, Duke University

Brief Summary:
REMD-477 (Volagidemab) is a human anti-glucagon receptor antibody. Its proposed mechanism of action in controlling hyperglycemia is by blocking glucagon receptor (GCGR) signaling. In this way, it increases hepatic glucose uptake, decreases hepatic glycogenolysis and gluconeogenesis, increases glycogen synthesis, and ultimately decreases blood glucose levels. This protocol will test the hypotheses that REMD-477 is safe and tolerable in patients with severe hyperglycemia on apelisib and prevent hyperglycemia associated with alpelisib in patients with advanced breast cancer who discontinue alpelisib due to severe hyperglycemia despite appropriate medical management.

Condition or disease Intervention/treatment Phase
Hyperglycemia Drug Induced Biological: REMD-477 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (GRIP-IT PILOT)
Actual Study Start Date : November 13, 2020
Estimated Primary Completion Date : November 13, 2023
Estimated Study Completion Date : November 13, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hyperglycemia
Drug Information available for: Glucagon

Arm Intervention/treatment
Experimental: REMD-477
REMD-477 (human IgG2 anti-glucagon receptor antibody Volagidemab) will be administered as a subcutaneous injection for four weekly doses
Biological: REMD-477
REMD-477 will be administered as a subcutaneous injection for four weekly doses
Other Name: Volagidemab




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 28 days ]
    Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor

  2. Serious Adverse Events [ Time Frame: 28 days ]
    Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor



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:

  • Locally advanced (not amenable to curative surgery) or metastatic invasive breast cancer
  • Age > 18 years
  • Post-menopausal or pre/peri-menopausal women prescribed ovarian suppression or men prescribed Lupron are permitted to participate
  • Histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory
  • HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization test (FISH, CISH, or SISH) is required.
  • Presence of one or more PIK3CA mutations in tumor tissue or plasma specimens
  • Participant is eligible to receive alpelisib and fulvestrant as per current FDA labeling
  • Participant has experienced grade 3 or 4 hyperglycemia during treatment with alpelisib (any cycle) despite standard of care measures (e.g metformin) leading to discontinuation of alpelisib.
  • ECOG performance status 0, 1 or 2
  • Ability to understand and the willingness to sign a written informed consent document
  • Participants must have normal organ and marrow function as defined below:

    • Leukocytes > 3,000/mm3
    • Absolute neutrophil count > 1,500/mm3
    • Platelets > 100,000/mm3
    • Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN
    • AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal; Creatinine ≤1.5 x institutional upper limit of normal OR creatinine clearance >L/min/1.73 m2 for subjects with creatinine levels above institutional normal.

Exclusion Criteria:

  • Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment
  • Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to therapy, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 25% of the bone marrow was irradiated
  • Established diagnosis of diabetes mellitus type 1 or uncontrolled type 2 diabetes (fasting plasma glucose level,>140 mg per deciliter or a glycosylated hemoglobin level of >6.4%)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alpelisib
  • Known brain metastases.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to alpelisib or other agents used in this study.
  • Receiving any medications or substances that are strong CYP3A4 inducers.
  • A history or family history of pancreatic neuroendocrine tumors, multiple endocrine neoplasia or pheochromocytoma
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study.
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy)

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): NCT04330625


Contacts
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Contact: Susan Dent, MD 919 684 5734 susan.dent@duke.edu
Contact: Keiana Watkins, MPH (919) 660-1278 keiana.watkins@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Susan Dent, MD       susan.dent@duke.edu   
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Susan Dent, MD Duke University
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Responsible Party: Herbert Lyerly, Professor, Duke University
ClinicalTrials.gov Identifier: NCT04330625    
Other Study ID Numbers: Pro00105104
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: November 20, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Herbert Lyerly, Duke University:
hyperglycemia
anti-glucagon receptor antibody
breast cancer
PI3 Kinase
Volagidemab
Additional relevant MeSH terms:
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Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
REMD-477
Hypoglycemic Agents
Physiological Effects of Drugs