Clinical Trials /

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

NCT04330625

Description:

REMD-477 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy
  • Official Title: A Pilot Study of Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (GRIP-IT PILOT)

Clinical Trial IDs

  • ORG STUDY ID: Pro00105104
  • NCT ID: NCT04330625

Conditions

  • Hyperglycemia Drug Induced

Interventions

DrugSynonymsArms
REMD-477REMD-477

Purpose

REMD-477 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.

Trial Arms

NameTypeDescriptionInterventions
REMD-477ExperimentalREMD-477 (human IgG2 anti-glucagon receptor antibody) will be administered as a subcutaneous injection for four weekly doses
  • REMD-477

Eligibility 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events
Time Frame:28 days
Safety Issue:
Description:Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Duke University

Trial Keywords

  • hyperglycemia
  • anti-glucagon receptor antibody
  • breast cancer
  • PI3 Kinase

Last Updated

March 31, 2020