Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05967884
Other study ID # OMS 05-2023
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date August 4, 2023
Est. completion date August 1, 2024

Study information

Verified date July 2023
Source Ottawa Hospital Research Institute
Contact Angel Arnaout, MD
Phone 613-798-5555
Email anarnaout@toh.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This proposal is for a Window of Opportunity (WOO) clinical trial using a novel combination of two Health Canada approved agents, cemiplimab (Libtayo) and dupilumab (Dupixent), for off label use in early-stage estrogen receptor positive (ER+) breast cancer.


Description:

This is a phase II, open-label, randomized window of opportunity trial evaluating the immunologic effects within the tumour, microenvironment, and host blood of patients treated with either - Arm A: Cemiplimab (n=10) - Arm B: Cemiplimab + Dupilumab (n=10) administered prior to surgery. Randomization will be at 1:1 ratio in patients newly diagnosed with primary operable ER+* HER2- invasive breast cancer awaiting surgery in the next 4-6 weeks who are not planned for neoadjuvant therapy. Primary Hypothesis: In ER+ breast cancer, blockade of IL-4 signalling using dupilumab enhances anti-tumor immunity (through reduced Th2 skewing) when used in combination with PD-1 inhibitors (Cemiplimab) compared to PD-1 inhibition alone in ER+ breast cancer Primary Objective: • To determine whether addition of dupilumab to cemiplimab reduces TH2 skewing of the tumor, tumor microenvironment (TME) and blood in patients with ER+ breast cancer Secondary Objectives: - To evaluate dynamic changes in immune cell populations as measured by in situ proteomics - To characterize the safety of a short-term duration of the combination of dupilumab with cemiplimab in patients with ER+ breast cancer awaiting surgery Exploratory Objective: • To test the effect of tumor PD-1 gene expression and its effect on the immune response in treated and untreated patients This is a window of opportunity trial which will require administration of cemiplimab or combination of cemiplimab + dupilumab prior to surgery. Surgery will be a minimum of 96 hours to 2 weeks after the cemiplimab. Patient follow-up after surgery will be for a period of 30 days post-surgery. Target: 20 patients (10 in Arm A and 10 in Arm B). Accounting for screen failures and withdrawals (20%), 24 patients will be accrued.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 20
Est. completion date August 1, 2024
Est. primary completion date August 1, 2024
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria: 1. Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery. 2. Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS) 3. ER+ breast cancer (1-10%*) of any size. ER positive tumor defined =1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines. 4. The participant is eligible for surgery within the next 4-6 weeks. 5. HER2/neu must be negative by immunohistochemistry (IHC) defined as IHC 0 or 1+ or fluorescence in situ hybridization (FISH) or other ISH methods with a ratio of < 2 according to current ASCO (American Society of Clinical Oncology)/CAP guidelines. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 7. Age =18 years. 8. The participant (or legally acceptable representative if applicable) is able to provide written informed consent for the study. Exclusion Criteria: 1. Known or suspected breast cancer metastasized to distant organ (lung, liver, bone, brain, abdomen) 2. Prior therapy with any chemotherapy or endocrine for breast cancer or other cancers within last 3 months 3. Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive carcinoma NOS. 4. Patients with an active infection or an absolute neutrophil count < 1.5 x 10^9/L. 6. Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m2. 7. Known or current history of pneumonitis or interstitial lung disease (e.g., idiopathic pulmonary fibrosis) or pneumonia in past month 8. Has known HIV or active Hepatitis B (e.g., HBV detected by PCR, presence of HBsAg surface antigen and/or Anti-HBc core antigen) or active Hepatitis C (e.g., HCV RNA [qualitative] is detected). Presence of Anti-HBs alone suggesting immunity to Hepatis B is eligible. 9. Any serious known immediate or delayed hypersensitivity reaction(s) to dupilumab and or cemiplimab. 10. Concurrent medical condition requiring the use of systemic immunosuppressive medications, or systemic corticosteroids at doses of greater than 10 mg Prednisone-equivalent. Topical steroids and other localized corticosteroids are permitted. Patients who have received acute, low-dose, systemic immunosuppressant medications equivalent to = 10mg of prednisone within the 7 days prior to study entry (small dose of dexamethasone for nausea, short course for upper respiratory tract infection etc.) may be enrolled in the study. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted. 11. Concurrent use or planned use of any forbidden medications within 4 weeks prior to study drug administration, which include chemotherapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control cancers), other biologic therapy, investigational therapy, or hormonal therapy. 12. Confirmed pregnancy (by pregnancy test) if patient is of childbearing age or breast feeding. 13. Subjects with signs/symptoms suggestive of COVID-19 and confirmed positive COVID-19 test. 14. Eastern Cooperative Oncology Group (ECOG) performance status =3 (see Appendix) 15. Any underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events, or renders the patient ineligible to be on study.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Arm A: Cemiplimab, Arm B: Cemiplimab + Dupilumab
Arm A: Cemiplimab: 350mg IV x 1 dose administered prior to surgery Arm B: Cemiplimab + Dupilumab: Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery

Locations

Country Name City State
Canada The Ottawa Hospital Research Institute and Cancer Center Ottawa Ontario
Canada Ontario Institute for Cancer Research Toronto Ontario

Sponsors (2)

Lead Sponsor Collaborator
Ottawa Hospital Research Institute Ontario Institute for Cancer Research

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other PD-1 Gene Expression PD-1 Gene expression analysis in pre treatment tissue samples expression and its effect on the immune response in treated and untreated patients up to 6 months
Primary Immune Cell Population Analysis The % change in various immune cell populations (CD3, CD8, macrophages and DC cells) in the tumor and microenvironment, Defined as the post-treatment value / pre-treatment value * 100% up to 6 months
Secondary Study Participant Assessment of Adverse Effects Number of participants with treatment-related adverse effects of patients treated with short term cemiplimab + dupilumab, using NCI-CTCAE up to 6 months
See also
  Status Clinical Trial Phase
Recruiting NCT04681911 - Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer Phase 2
Terminated NCT04066790 - Pyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer Phase 2
Completed NCT04890327 - Web-based Family History Tool N/A
Completed NCT03591848 - Pilot Study of a Web-based Decision Aid for Young Women With Breast Cancer, During the Proposal for Preservation of Fertility N/A
Recruiting NCT03954197 - Evaluation of Priming Before in Vitro Maturation for Fertility Preservation in Breast Cancer Patients N/A
Terminated NCT02202746 - A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer Phase 2
Active, not recruiting NCT01472094 - The Hurria Older PatiEnts (HOPE) With Breast Cancer Study
Completed NCT06049446 - Combining CEM and Magnetic Seed Localization of Non-Palpable Breast Tumors
Withdrawn NCT06057636 - Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study N/A
Recruiting NCT05560334 - A Single-Arm, Open, Exploratory Clinical Study of Pemigatinib in the Treatment of HER2-negative Advanced Breast Cancer Patients With FGFR Alterations Phase 2
Active, not recruiting NCT05501769 - ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer Phase 1
Recruiting NCT04631835 - Phase I Study of the HS-10352 in Patients With Advanced Breast Cancer Phase 1
Completed NCT04307407 - Exercise in Breast Cancer Survivors N/A
Recruiting NCT03544762 - Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation Phase 3
Terminated NCT02482389 - Study of Preoperative Boost Radiotherapy N/A
Enrolling by invitation NCT00068003 - Harvesting Cells for Experimental Cancer Treatments
Completed NCT00226967 - Stress, Diurnal Cortisol, and Breast Cancer Survival
Recruiting NCT06019325 - Rhomboid Intercostal Plane Block on Chronic Pain Incidence and Acute Pain Scores After Mastectomy N/A
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT06037954 - A Study of Mental Health Care in People With Cancer N/A