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

Sponsor

Duke University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04330625

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Nov 13, 2020

Anticipated Primary Completion Date :

Nov 13, 2023

Anticipated Study Completion Date :

Nov 13, 2023

Arms and Interventions

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 Names: Volagidemab

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 Names:

Volagidemab

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)