A Study to Prevent Rash in People Starting Alpelisib for the Treatment of Breast Cancer

RETENTION: An Open-Label Phase 2 Trial of InteRlEukin (5) InhibiTion for the prEveNTION of Alpelisib Rash in Metastatic PIK3CA-mutant Hormone-Receptor Positive Breast Cancer

The researcher are doing this study to find out whether benralizumab is effective at preventing skin rashes caused by alpelisib in people who have metastatic breast cancer. Skin rash is a common side effect of alpelisib. Researchers think adding benralizumab to the standard-of-care hormone treatment and alpelisib may prevent the patient from getting a rash.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Benralizumab; Drug: fulvestrant or AIs) and PI3K inhibition (alpelisib)

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center (All protocol activities)
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Rockville (Limited Protocol Activities)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed metastatic HR-positive, HER2-negative breast cancer. HR positive is defined by ER status >10% immunohistochemical (IHC) staining of any intensity.
2. Must be scheduled to receive SOC endocrine therapy (alpelisib plus fulvestrant or AIs)
3. Presence of one or more activating PIK3CA mutations in tumor tissue.
4. Measurable disease per RECIST v1.1 OR at least one predominantly lytic bone lesion must be present.
5. Written informed consent provided
6. Female or male ≥18 years of age
7. Eastern Cooperative Oncology Group performance status of 0 or 1.
8. Life expectancy ≥6 months.

9. Adequate organ and marrow function as defined below:

   • Hemoglobin ≥8.0 g/dL (without blood transfusion within 7 days of laboratory test used to determine eligibility)
   • Absolute neutrophil count ≥1.0 × 10^9 /L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
   • Platelet count ≥50 × 10^9 /L (without transfusion within 2 weeks of laboratory test used to determine eligibility)
   • Total bilirubin (TB) ≤1.0 × institutional upper limit of normal (ULN; Patients with known Gilbert's disease who have TB ≤3 × ULN may be enrolled)
   • Aspartate transaminase/alanine transaminase ≤2.5 × ULN with normal alkaline phosphatase (≤5 × ULN for patients with liver metastases) OR ≤1.5 × ULN in conjunction with alkaline phosphatase >2.5 × ULN
   • Creatinine ≤1.5 mg/dL
10. Able to swallow oral medication.
11. Willing to be randomized to any of the treatment arms and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.

12. Women must be of postmenopausal status. Postmenopausal status is defined by any one of the following criteria:

    • Prior bilateral oophorectomy
    • Age ≥60 years
    • Age <60 years and amenorrheic for at least 12 months (spontaneous cessation of menses for 12 consecutive months or more in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone and estradiol levels in the postmenopausal range without an alternative cause.

Exclusion Criteria:

1. Known hypersensitivity to alpelisib, fulvestrant or AIs, benralizumab, cetirizine, or to any of the excipients of alpelisib, fulvestrant or AIs, benralizumab, or cetirizine.
2. Concurrent malignancy (basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical cancer in situ that have undergone curative intent therapy are allowed)
3. Individuals with impaired decision making capacity.
4. Concurrent use of another investigational drug or device for the rash (i.e., outside of study treatment) during, or within 4 weeks of treatment.
5. Known use of anti-IL-5 agents or other biologics for the treatment of asthma which are known to decrease blood eosinophil levels within the past 12 weeks.
6. Known history of anaphylaxis to benralizumab therapy.
7. A helminthic parasitic infection diagnosed within 24 weeks prior to the first treatment, and assent when applicable, was obtained that had not been treated with, or has failed to respond to, standard of care therapy.
8. Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
9. Active infection that would impair the ability of the patient to receive study treatment.
10. Women who are pregnant or breast-feeding.
11. Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
12. Oral corticosteroids at a dose of ≥20mg/day prednisone or equivalent within 14 days expected to continue during alpelisib therapy.
13. More than 2 lines of endocrine-based therapy in the metastatic setting.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab and PI3K inhibition (alpelisib); Patients will receive fulvestrant or AIs and PI3K inhibition (alpelisib) per SOC (fulvestrant on days 1, 15, 29 and monthly thereafter; Ais on a daily continuous basis). Participants will receive one injection of benralizumab 30mg subcutaneously on day -1.	Drug: Benralizumab; Benralizumab 30mg subcutaneously on day -1.; Drug: fulvestrant or AIs) and PI3K inhibition (alpelisib); SOC endocrine therapy (fulvestrant or AIs) and PI3K inhibition (alpelisib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Subjects That Have a Grade ≤1 Rash	4 weeks

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: AstraZeneca; Novartis Pharmaceuticals
• Investigators: Principal Investigator: Alina Markova, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Actual): August 2, 2024
• Study Completion (Actual): August 2, 2024

Study Registration Dates

• First Submitted: July 20, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Benralizumab; HER2-negative breast cancer; Rash; Alpelisib; Metastatic HR-positive; 22-276
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Asthmatic Agents; Respiratory System Agents; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Benralizumab; Fulvestrant
• Other Study ID Numbers: 22-276

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No