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A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study

NCT04215146

Description:

The purpose of this study is to find out the possible anti-cancer effect of pelareorep in combination with chemotherapy [paclitaxel] and avelumab in treating a type of breast cancer called Hormone Receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 negative(HER2-) breast cancer, which is either locally advanced or has metastasized (cancer that has spread in your body). The study will investigate if pelareorep in combination with paclitaxel and avelumab is more effective than paclitaxel alone, or pelareorep and paclitaxel. The safety of the combination treatments will also be evaluated.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study
  • Official Title: A Study to Assess Overall Response Rate by Inducing an Inflammatory Phenotype in Metastatic BReast cAnCEr With the Oncolytic Reovirus PeLareorEp in CombinaTion With Anti-PD-L1 Avelumab and Paclitaxel - BRACELET-1 Study

Clinical Trial IDs

  • ORG STUDY ID: REO 028
  • SECONDARY ID: PrE0113
  • NCT ID: NCT04215146

Conditions

  • Breast Cancer Metastatic

Interventions

DrugSynonymsArms
PaclitaxelCohort 1
PelareorepCohort 2
AvelumabCohort 3

Purpose

The purpose of this study is to find out the possible anti-cancer effect of pelareorep in combination with chemotherapy [paclitaxel] and avelumab in treating a type of breast cancer called Hormone Receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 negative(HER2-) breast cancer, which is either locally advanced or has metastasized (cancer that has spread in your body). The study will investigate if pelareorep in combination with paclitaxel and avelumab is more effective than paclitaxel alone, or pelareorep and paclitaxel. The safety of the combination treatments will also be evaluated.

Detailed Description

      This is an open-label randomized Phase 2, 3-cohort study to evaluate the safety and efficacy
      of pelareorep, paclitaxel and avelumab in Hormone Receptor+ (HR+)/Human Epidermal Growth
      Factor Receptor 2 negative (HER2-) with endocrine-refractory metastatic breast cancer.

      Patients will be randomized to one of three treatment cohorts: paclitaxel alone, pelareorep +
      paclitaxel, or pelareorep + paclitazel + avelumab. A three patient safety run-in will be
      conducted in the cohort for pelareorep + paclitazel + avelumab prior to beginning
      randomization into all three cohorts.

      Patients will give mandatory blood samples and optional tumor biopsies, which will be
      analyzed for biomarkers to determine the immunological changes within the tumor
      microenvironment and peripheral blood in patients treated with paclitaxel alone, in
      combination with pelareorep, and in combination with pelareorep and avelumab.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1Active ComparatorPatients receive paclitaxel alone.
  • Paclitaxel
Cohort 2ExperimentalPatients receive pelareorep + paclitaxel.
  • Paclitaxel
  • Pelareorep
Cohort 3ExperimentalPatients receive pelareorep + paclitaxel + avelumab.
  • Paclitaxel
  • Pelareorep
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          1. Female patients ≥ 18 years of age at the time of signing the informed consent form
             (ICF).

          2. Must have a histological/cytological diagnosis of breast cancer. Disease must be:

               -  Positive for estrogen receptor (ER) and/or progesterone receptor (PgR) as defined
                  by

                  ≥ 1% tumor cell nuclei immunoreactive.

               -  Negative for HER2 amplification / overexpression as defined per the American
                  Society of Clinical Oncology - College of American Pathologists (ASCO-CAP)
                  guidelines. However, patients with HER2 equivocal disease for whom HER2 targeted
                  therapy isn't indicated are also eligible for enrollment.

          3. ECOG performance status of 0-1

          4. Must have unresectable locally advanced or metastatic disease, for which no curative
             therapy exists and for which systemic chemotherapy is indicated.

          5. Measurable disease as defined by RECIST Version 1.1

          6. Prior Hormonal Therapy:

               -  Patients must have progressed on at least 1 hormone-based therapy with a CDK4/6
                  inhibitor. Patients who received a CDK4/6 inhibitor in the adjuvant setting and
                  progressed while on or within 6 months of discontinuation of CDK4/6 inhibitor
                  therapy are eligible.

               -  Prior mTOR inhibitor therapy is allowed but is not required.

          7. Ability to understand and willingness to sign IRB-approved informed consent.

          8. Willing to provide blood samples for research

          9. Adequate organ function as measured by the following criteria, obtained ≤ 2 weeks
             prior to registration:

             Hematology:

               -  Neutrophils ≥ 1.5 x 10^9/L

               -  Platelets ≥ 100 x 10^9/L

               -  Lymphocytes ≥ 0.8 x 10^9/L

               -  INR < 1.5x ULN (Unless on therapeutic anticoagulation)

               -  PTT < 1.5x ULN

             Biochemistry:

               -  Serum Creatinine ≤ 1.5x ULN

               -  Total Bilirubin ≤ 1.0x ULN (unless due to Gilbert's Disease and direct bilirubin
                  <ULN)

               -  ALT and AST ≤ 3x ULN (Note: ≤ 5x ULN if documented liver metastasis)

               -  Proteinuria ≤ Grade 2* (using spot testing; if Grade 3 repeat with mid-stream
                  urine; if still Grade 3 then urine collection for 24 hours to confirm Grade 0, 1
                  or 2) *as per National Cancer Institute Common Terminology Criteria for Adverse
                  (NCI-CTCAE)

         10. Women must not be pregnant or breastfeeding since we do not know the effects of the
             study drugs on the fetus or breastfeeding child. All sexually active females of
             childbearing potential (not surgically sterilized and between menarche and 1 year post
             menopause) must have a blood test to rule out pregnancy within 2 weeks prior to
             registration.

         11. Sexually active women of child-bearing potential with a non-sterilized male partner
             must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2
             barrier forms) OR abstinence prior to study entry, for the duration of study
             participation, and for 3 months following last dose of study drugs. Method of
             contraception must be documented. NOTE: If a woman become pregnant or suspect she is
             pregnant while participating in this study, she must inform her treating physician
             immediately.

        Exclusion Criteria:

          1. No major surgery within 21 days prior to beginning study treatment. Major surgery >21
             days prior to beginning study treatment is permitted provided that the patient has
             recovered adequately to receive systemic chemotherapy. NOTE: Placement of a vascular
             access device is not considered major surgery.

          2. Patients who have received radiation treatment within 14 days of beginning study
             treatment are excluded. Patients who have received palliative radiation ≥ 14 days
             prior to beginning study treatment may enroll if they have recovered from all local
             and systemic side effects to ≤ Grade 1 (NCI-CTCAE).

          3. No prior chemotherapy in the advanced/metastatic setting is allowed. Patients may have
             received chemotherapy in the (neo)adjuvant setting. Patients receiving (neo)adjuvant
             taxanes must have a disease-free interval of at least 12 months.

          4. No known active, uncontrolled or symptomatic Central Nervous System (CNS) metastases,
             carcinomatous meningitis, or leptomeningeal disease as indicated by clinical
             symptoms,cerebral edema, and/or progressive growth. Patients with CNS metastases
             treated with radiation therapy (Whole-Brain Radiation Therapy [WBXRT] or Stereotactic
             Radiotherapy [SRS]) are eligible if, >28 days following completion of XRT, they show
             stable disease on post-treatment MRI/CT, are off corticosteroids, and are
             neurologically stable.

          5. No known history of other malignancies, except for adequately treated non-melanoma
             skin cancer or solid tumors curatively treated with no evidence of disease for >3
             years.

          6. Not on chronic immunosuppressive therapy including, but not exclusively, steroids (≥
             10 mg prednisone a day or equivalent) or monoclonal antibodies, chronic methotrexate
             or cyclophosphamide, tacrolimus or sirolimus.

          7. No known HIV infection. Testing not required in absence of clinical suspicion.

          8. No known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection or
             undergoing anti-viral treatment. Testing for HBV/HCV is not required in absence of
             clinical suspicion.

          9. No concurrent disease or condition that would interfere with study participation or
             safety,such as any of the following:

             • Active, clinically significant infection either Grade >2 by CTCAE V5.0 or requiring
             the use of parenteral anti-microbial agents within 14 days before registration.

         10. No active or history of any autoimmune disease (patients with diabetes Type 1,
             vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive
             treatment are eligible) or immunodeficiencies.

         11. Patients may not have evidence of uncontrolled cardiovascular conditions, including
             uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive
             heart failure (New York Heart Association [NYHA] Class III or higher), unstable
             angina, or myocardial infarction within the past 6 months prior to registration. NOTE:
             Patients with asymptomatic rate-controlled atrial fibrillation may participate.

         12. Patients may not have other significant diseases (for example, inflammatory bowel
             disease), which, in the opinion of the Investigator, might impair the patient's
             tolerance of trial treatment.

         13. Patients with a known allergy to any of the study medications, their analogues, or
             excipients in the various formulations of any agent are not eligible.

         14. Patients who have contraindications to treatment with paclitaxel and/or neuropathy
             >Grade 2 are not eligible.

         15. Patients who have not recovered from clinically significant acute toxicities of
             previous therapy are not eligible, except treatment-related alopecia or stable sensory
             neuropathy ≤ Grade 2.

         16. No prior therapy with any investigational anti-cancer therapy within 30 days. Prior
             immunotherapies are prohibited.

         17. No prior therapy with checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies),
             checkpoint agonist agents (e.g., anti-GITR, anti-OX40 antibodies) and/or another
             active immunotherapy in breast cancer such as cancer vaccines or oncolytic virsus.

         18. Patients with any serious medical or psychiatric illness that could, in the
             Investigator's opinion, potentially interfere with the completion of the treatment
             according to the protocol, are not eligible.

         19. Patients with legal incapacity or limited legal capacity are not eligible.

         20. Patients with known alcohol or drug abuse are not eligible.

         21. Patients may not participate in any other therapeutic clinical trials, including those
             with other investigational agents not included in this trial, throughout the duration
             of this study.

         22. Patients may not have non-oncology vaccine therapies for prevention of infectious
             disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4
             weeks of study drug administration. Vaccination while on study is also prohibited
             except for administration of the inactivated influenza vaccine.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:at week 16.
Safety Issue:
Description:Overall response rate at week 16 according to RECIST V1.1.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Oncolytics Biotech

Trial Keywords

  • Breast
  • Breast Cancer
  • Breast Cancer Metastatic
  • Locally Advanced Breast Cancer
  • Pelareorep
  • Avelumab
  • Paclitaxel
  • Reovirus
  • Oncolytic virus
  • HR+ breast cancer
  • HER2- breast cancer
  • Breast malignancy

Last Updated

December 28, 2019