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

  • STATUS
    Recruiting
  • End date
    Nov 13, 2023
  • participants needed
    9
  • sponsor
    Duke University
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Updated on 25 November 2021
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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.

Details
Condition Hyperglycemia Drug Induced
Treatment REMD-477
Clinical Study IdentifierNCT04330625
SponsorDuke University
Last Modified on25 November 2021

Eligibility

 Yes No Not Sure

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)
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