Testing of a new drug, Avelumab, in patients with breast cancer

Phase 1

• Conditions: High risk triple negative (ER negative, PR negative, HER2 negative) breast cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000189-45-GB
• Lead Sponsor: niversity of Padova

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-19
• Last Update Posted: 3 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 474

Inclusion Criteria

-Male/female aged>18 years
-Signed informed consent
-ECOG performance status 0/1
-Non-metastatic histologically confirmed primary invasive breast carcinoma
-Normal organ & marrow function
-Highly effective contraception for male & female subjects (from 28 days prior to trial treatment to at least 60 days after stopping trial treatment)
- FFPE block containing tumor tissue or at least 7 unstained tumor slides

Specific Stratum A:
-TNBC: hormone receptor (ER<10% & PgR<10%) & HER2 negative (IHC0/1+ or ISH non-amplified). If discordance between pre-operative core-biopsy & surgical sample, receptor assessment on surgical sample has to be considered for inclusion criteria evaluation
-Completed treatment with curative intent including surgery & adjuvant chemotherapy
-Adequately excised: have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy. Margins of resected specimen should be free of invasive tumor & ductal carcinoma in situ (CIS). In the case of breast-conserving surgery patients with margins positive for lobular CIS are eligible without additional resection. Patients who undergo mastectomy or with a microscopic positive deep margin are eligible, provided radiotherapy on chest wall is planned.
-Had axillary lymph node (LN) dissection for evaluation of pathologic nodal status. Must meet 1 of:
a.if 4 or more metastatic LN, any pT
b.if 1 to 3 metastatic LN, pT>2cm
c.if no metastatic LN, pT>5cm
-Had adjuvant chemotherapy after surgery. Adjuvant treatment should have included at least 3courses of an anthracycline agent & 3courses of a taxane agent. Patients who cannot complete all planned treatment cycles for any reason are considered high risk & therefore are eligible for the study. Patients who received dose-dense regimens & those who received carboplatin as part of the adjuvant treatment are eligible
-No more than 10weeks may elapse between the completion adjuvant chemotherapy&randomization

Specific Stratum B:
-TNBC: hormone receptor negative (ER < 10% & PgR < 10%) & HER2 negative (IHC 0/1+ or ISH non-amplified), as defined by the local pathology laboratory. In case of discordance between the pre-treatment diagnostic core-biopsy and the surgical sample, the receptor assessment performed on the surgical sample has to be considered for inclusion criteria evaluation.
-Patients must have completed treatment with curative intent including: neoadjuvant chemotherapy & surgery
-Adequately excised: patients should have undergone adequate tumor excision after preoperative chemotherapy, which means surgical removal of all clinically evident disease in the breast & LN’s
a.Must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy. Margins of resected specimen should be free of invasive tumor & ductal CIS. In the case of breast-conserving surgery patients with margins positive for lobular CIS are eligible without additional resection. Patients who undergo mastectomy, patients with a microscopic positive deep margin are eligible, provided radiotherapy on chest wall is planned
b.LN surgery:
-Axillary dissection without sentinel node evaluation is permitted after preoperative therapy
-If positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy(SNB) performed prior to preoperative therapy, additional surgical evaluation of the axilla following preoperative therapy is required
-If SNB performed before preoperative therapy was negativ

Exclusion Criteria

1.Metastatic breast cancer.
2.Synchronous bilateral breast cancer, unless both tumors confirmed triple negative disease.
3.History of non-breast malignancies within the 5 years prior to study entry, except for the following: Carcinoma in situ (CIS) of the cervix, CIS of the colon, Basal cell and squamous cell carcinomas of skin.
4.Prior organ transplantation, including allogeneic stem-cell transplantation.
5.Prior or concomitant treatment with any other investigational agents.
6.Prior therapy with any antibody / drug targeting T-cell coregulatory proteins (immune
checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
7.Concurrent anticancer treatment (e.g. cytoreductive therapy, immune therapy, cytokine therapy except for erythropoietin). If indicated, radiotherapy to the operated breast/chest wall/locoregional lymph nodes is admitted
8.Concomitant treatment with all herbal (alternative) remedies with immunostimulating properties (for example, mistletoe extract) or known to potentially interfere with major organ function (e.g. hypericin)
9.Major surgery for any reason, within 4 weeks of randomization and / or if the subject has not fully recovered from the surgery within 4 weeks of randomization
10.Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to = 10 mg prednisone daily)
11.Significant acute or chronic infections including, among others:
a.Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
b.Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
12.Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent:
a.Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b.Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses = 10 mg or equivalent prednisone per day
13.Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
14.Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be = 10 mg per day of equivalent prednisone
15.Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
16.Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident /stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (New York Heart Association Classification Class = II), or serious uncontrolled cardiac arrhythmia requiring medication
17.All other significant diseases (for example, inflammatory bowel disease), which, in the op

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified