Hyperglycemia Drug InducedPhase 1NCT04330625
Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (REMD-477)
A Phase 1 study testing REMD-477 in people with Hyperglycemia Drug Induced, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperglycemia Drug Induced
- What is being tested?
- REMD-477
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Nov 2020to 5 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Pilot Study of Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (GRIP-IT PILOT)
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.
- Conditions
- Hyperglycemia Drug Induced
- Being tested
- REMD-477
- Keywords
- hyperglycemia, anti-glucagon receptor antibody, breast cancer, PI3 Kinase, Volagidemab
- Medical subject headings
- Hyperglycemia, Breast Neoplasms, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REMD-477Biological
Also called Volagidemab
REMD-477 will be administered as a subcutaneous injection for four weekly doses
| Study group | Role | What they receive |
|---|---|---|
| REMD-477 | Experimental | REMD-477 (human IgG2 anti-glucagon receptor antibody Volagidemab) will be administered as a subcutaneous injection for four weekly doses Receives: Biological: REMD-477 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor
Measured: 28 days
Serious Adverse Events
Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start13 Nov 2020
- Primary completion5 May 2021
- Study completion5 May 2021
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperglycemia Drug InducedStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Herbert Lyerly, Duke University
- Investigators
- Susan Dent, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04330625
- Sponsor's protocol ID
- Pro00105104
- Status last verified
- Nov 2022
- First submitted
- 31 Mar 2020
- Last updated
- 8 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Glucagon Receptor Inhibition to Enable Breast Cancer Patients to Benefit From PI3K Inhibitor Therapy (GRIP-IT PILOT)
- ClinicalTrials.gov ID
- NCT04330625
- Acronym / sponsor ID
- Pro00105104
- Conditions
- Hyperglycemia Drug Induced
- Keywords
- hyperglycemia, anti-glucagon receptor antibody, breast cancer, PI3 Kinase, Volagidemab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 5 May 2021 (actual)
- Study completion
- 5 May 2021 (actual)
- First posted
- 1 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| REMD-477 | Experimental | Biological: REMD-477REMD-477 (human IgG2 anti-glucagon receptor antibody Volagidemab) will be administered as a subcutaneous injection for four weekly doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REMD-477Also: VolagidemabREMD-477 will be administered as a subcutaneous injection for four weekly doses | Biological | REMD-477 |
Primary outcome
Adverse Events
Time frame: 28 days
Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor
Serious Adverse Events
Time frame: 28 days
Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor
Results and safety
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Dent, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing REMD-477 in people with Hyperglycemia Drug Induced, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.