A Window-of-opportunity Study of Pelareorep in Early Breast Cancer

NCT ID: NCT04102618

Last Updated: 2022-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

EARLY_PHASE1

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-29

Study Completion Date

2022-04-20

Brief Summary

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The purpose of this study is to find out if pelareorep in combination with different therapies helps to reduce the growth of breast cancer cells and increase the immune system's response to cancer. This study will also help to understand what this treatment does to the tumor. In addition, the safety of the combination treatments with pelareorep will be evaluated.

Detailed Description

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This is a window of opportunity non-randomized exploratory study to evaluate the safety and anti-tumor immunogenicity of pelareorep -/+ atezolizumab in five different cohorts in women with operable early breast cancer.

After enrollment, pelareorep will be administered at 4.5 × 1010 TCID50 intravenously on days 1, 2, 8 \& 9. Other therapies will be administered according to the assigned treatment cohort.

After an initial biopsy (diagnostic biopsy in most cases), a second biopsy will be performed on Day 3. Patients will continue the planned treatment until day 21(±5), when a third biopsy will be performed. This third biopsy can be the surgical specimen if patient was scheduled for primary surgery, or a core biopsy if patient will undergo neoadjuvant treatment.

Blood samples will be collected throughout the study at three time points, Day 1, Day 3, and End of Treatment.

Patients will receive treatment for 3 weeks prior to surgery or neoadjuvant therapy. Thereafter, patients will either be considered for definitive surgery or primary medical treatment (e.g. neoadjuvant chemotherapy) at the discretion of the treating physician. Surgery or biopsy prior to neoadjuvant chemotherapy should be done within 3 weeks (±5 days) from the start of the study treatment.

The end of study visit will be performed at the day of surgery. A safety follow-up, the end of study visit, will be done at 28 days (± 7 days) after the last dose of treatment received

Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 (closed to enrollment)

HR+/HER2-neg patients who will receive pelareorep plus letrozole

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Letrozole

Intervention Type DRUG

Oral dose of 2.5 mg/day starting on Day 3 for 13 days

Cohort 2 (closed to enrollment)

HR+/HER2-neg patients who will receive pelareorep plus letrozole plus atezolizumab

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Letrozole

Intervention Type DRUG

Oral dose of 2.5 mg/day starting on Day 3 for 13 days

Atezolizumab

Intervention Type DRUG

1200 mg administered intravenously on Day 3

Cohort 3 (closed to enrollment)

TNBC patients who will receive pelareorep plus atezolizumab

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Atezolizumab

Intervention Type DRUG

1200 mg administered intravenously on Day 3

Cohort 4 (closed to enrollment)

HER2+/HR+ patients who will receive pelareorep plus trastuzumab plus atezolizumab

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Atezolizumab

Intervention Type DRUG

1200 mg administered intravenously on Day 3

Trastuzumab

Intervention Type DRUG

8mg/kg administered intravenously or 600mg subcutaneously on Day 3

Cohort 5 (closed to enrollment)

HER2+/HR- patients who will receive pelareorep plus trastuzumab plus atezolizumab

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Atezolizumab

Intervention Type DRUG

1200 mg administered intravenously on Day 3

Trastuzumab

Intervention Type DRUG

8mg/kg administered intravenously or 600mg subcutaneously on Day 3

Cohort 6

HER2+ (irrespective of HR status) (6 patients) who will receive pelareorep + trastuzumab

Group Type EXPERIMENTAL

Pelareorep

Intervention Type BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Trastuzumab

Intervention Type DRUG

8mg/kg administered intravenously or 600mg subcutaneously on Day 3

Interventions

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Pelareorep

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Intervention Type BIOLOGICAL

Letrozole

Oral dose of 2.5 mg/day starting on Day 3 for 13 days

Intervention Type DRUG

Atezolizumab

1200 mg administered intravenously on Day 3

Intervention Type DRUG

Trastuzumab

8mg/kg administered intravenously or 600mg subcutaneously on Day 3

Intervention Type DRUG

Other Intervention Names

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Previously REOLYSIN®

Eligibility Criteria

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Inclusion Criteria

1. Signed written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures and assessments.
2. Female patients.
3. Age ≥18 years. In cohorts 1 and 2 (patients with HR+/HER2 negative breast cancer), only postmenopausal\* patient can be included.
4. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast, with all of the following characteristics:

* At least 1 lesion that can be measured in at least 1 dimension with ≥ 10 mm in largest diameter measured by ultrasound and mammogram.
* Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice. Routine exams to discard metastases will be performed according to Investigator judgement but are mandatory in case of suspicion of metastatic disease.
* Breast cancer eligible for primary surgery.
* In the case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be ≥ 10 mm and designated the "target" lesion for all subsequent tumor evaluations and biopsies.
5. Patient must have biopsiable disease.
6. Histologically confirmed HER2 status and hormone receptors (ER and PgR) according to ASCO/CAP guidelines locally assessed.

* Invasive TNBC defined as: ER and PR negative defined as IHC nuclear staining \<1% AND HER2 negative.
* HR+/HER2 negative defined as: ER and PR positive defined as IHC nuclear staining \>1% AND HER 2 negatives.
* HER2 positive defined as; IHC +++ or FISH positive.
7. ECOG Performance Status of 0 or 1.
8. Adequate organ function, as determined by the following laboratory tests, within 14 days prior to randomization:

* Hematological

* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Hemoglobin ≥ 9 g/dL (red blood cell transfusion and/or erythropoietin allowed)
* Renal

o Serum creatinine ≤ 1.5 x upper limit of normal (ULN), or 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN. (Note: Creatinine clearance does not need to be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard).
* Hepatic

* Serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 1.5 x ULN
* Aspartate aminotransferase (AST) ≤ 3 x ULN
* Alanine aminotransferase (ALT) ≤ 3 x ULN
* Coagulation International normalization ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN
* Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN
9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
10. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (only for cohorts 3 to 5 and pre-menopausal women or non-confirmed postmenopausal\* status).

* \*postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.) OR
* have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR
* has a congenital or acquired condition that prevents childbearing.

Exclusion Criteria

1. Inoperable locally advanced or inflammatory (i.e., inoperable Stage III) breast cancer.
2. Metastatic (Stage IV) breast cancer.
3. Bilateral invasive breast cancer.
4. Multicentric breast cancer, defined as the presence of two or more foci of cancer in different quadrants of the same breast.
5. Prior therapy for breast cancer.
6. Prior therapy with an anti- PD-1, anti- PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-CTLA-4 antibody compound, Pelareorep or any other oncolytic viruses.
7. Prior therapy with tumor vaccine
8. History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy or evidence of clinically significant immunosuppression. Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
9. Treated or untreated hyperthyroidism. Uncontrolled hypothyroidism (patients with controlled and asymptomatic hypothyroidism can be included)
10. Received any vaccine, including against SARS-COV-2 (COVID-19), \<14 days prior to the first day of study treatment. Inactivated vaccines (including against COVID-19 or seasonal influenza) are permitted after surgery.
11. History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome.
12. Evidence of clinically significant immunosuppression such as the following:

* diagnosis of immunodeficiency
* concurrent opportunistic infection
* receiving systemic immunosuppressive therapy (\> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses \> 10 mg/day of prednisone or equivalent. Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.
13. Cardiopulmonary dysfunction as defined by:

* Uncontrolled hypertension (systolic \>150 mm Hg and/or diastolic \> 100 mm Hg) despite optimal medical management.
* Inadequately controlled angina or serious cardiac arrhythmia not controlled by adequate medication.
* History of symptomatic congestive heart failure (CHF): Grade ≥ 3 per NCI CTCAE version 4.03 or Class ≥ II New York Health Association (NYHA criteria).
* Myocardial infarction within 6 months prior to randomization.
* Current dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
14. Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures).
15. Major surgical procedure or significant traumatic injury within approximately 28 days prior to enrollment or anticipation of the need for major surgery during the course of study treatment.
16. Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C.
17. Assessment by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
18. Known history of active Bacillus tuberculosis.
19. History of significant co-morbidities that, in the judgment of the Investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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SOLTI Breast Cancer Research Group

OTHER

Sponsor Role collaborator

Oncolytics Biotech

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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ICO Badalona

Badalona, , Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, , Spain

Site Status

Hospital Quirón Dexeus

Barcelona, , Spain

Site Status

Hospital Moisés Broggi

Esplugues de Llobregat, , Spain

Site Status

Hospital Fuenlabrada

Madrid, , Spain

Site Status

Hospital La Paz

Madrid, , Spain

Site Status

Hospital Puerta de Hierro de Majadahonda

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital Clínico Universitario Virgen Arrixaca

Murcia, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Instituto Valenciano de Oncología

Valencia, , Spain

Site Status

Hospital Clínico Lozano Blesa

Zaragoza, , Spain

Site Status

Countries

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Spain

Other Identifiers

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REO 027

Identifier Type: -

Identifier Source: org_study_id

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