Clinical trial NCT03144947: Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in HER2+ Breast Cancer Patients
Official title: Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients With Operable or Locally Advanced/Inflammatory HER2-positive Breast Cancer (ImmunHER)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cancer, Breast
Lead sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
Sponsor class: OTHER
Collaborators: name: University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit
name: University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology
name: University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione
name: Clirest s.r.l.
name: Mipharm SpA
name: Arithmos srl
name: Temas srl
First posted: 2017-05-09
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non comparative, multi-center, open-label, neoadjuvant, randomized study, the purpose of randomization is to reduce bias owing to patient selection into treatments groups.
Primary purpose: OTHER

Brief summary: Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients with Operable or Locally Advanced /Inflammatory HER2-positive Breast Cancer (ImmunHER)

Detailed description: Women with histologically confirmed HER2-positive breast cancer with locally advanced, inflammatory,or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.

Eligibility criteria: Inclusion Criteria:

* Previously untreated, infiltrating primary breast cancer with locally advanced, inflammatory, or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
* HER2 positivity (either immunohistochemistry 3+ or fluorescent in situ hybridization amplification).
* Age 18 or older.
* Eastern Cooperative Oncology Group performance status of 0 to 1.
* Availability of tumor tissue for biologic and molecular examination before starting primary treatment.
* Left ventricular ejection fraction within the institutional range of normal.
* Normal organ and marrow function.
* Adequate contraception methods for women of childbearing potential.
* Prior diagnosis of cancer is allowed as long as patient is free of disease and has been off treatment for the prior malignancy for a minimal interval of 3 years.
* Written informed consent.

Exclusion Criteria:

* Either stage I or IV breast cancer.
* Prior trastuzumab or pertuzumab.
* Any prior chemotherapy.
* Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
* Undergone major surgery (e.g., intrathoracic, intra-abdominal or intra-pelvic) 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery.
* Breast radiotherapy prior to starting study.
* Known hypersensitivity to the investigational drugs or any of their excipients.
* Evidence of any disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an GOIRC-01-2016 ImmunHER Protocol Version 1.0, 11 April 2016 Page 6 of 140 investigational drug, or puts the patient at high risk for treatment-related complications.
* Moderate/severe hepatic impairment (Child- Pugh B/C).
* Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Concurrent malignancy or malignancy within 3 years prior to study enrollment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or insitu carcinoma of the uterine cervix.
* Pregnancy or breastfeeding (breast feeding should be discontinued to be enrolled in the study).
* Women of childbearing potential that refusal to adopt adequate contraceptive measures.
* Unwilling or unable to comply with the protocol. -

Primary outcomes:
measure: Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph)
timeFrame: 6 months after last patient in
Secondary outcomes:
measure: Associations between biomarkers (TIL, Tumor specific lymphocyte cell activity (TLA), and Fc-gamma-R polymorphisms) and between each biomarker with clinical outcome variables.
timeFrame: at baseline, 6 months and 5 years after last patient in
measure: Frequency of toxicity Events: frequency of moderate and severe toxicity events and drop-out rate due to theraphy related toxicity (NCICommon Toxicity Criteria v 4.0)
timeFrame: 3.5 years
measure: HRQOL during study treatment based on FACT-B
timeFrame: at baseline, and 6 months after last patient in
measure: Complete pathological response rate by treatment arm
timeFrame: 6 months after last patient in
measure: 5-year disease-free survival by treatment arm between treatment arms
timeFrame: 5 years
Other outcomes:
Locations:
city: Cona
country: Italy
facility: UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara
state: Ferrara
city: Legnago
country: Italy
facility: UOC Oncologia Medica, Azienda ULSS21 di Legnago
state: Verona
city: Negrar
country: Italy
facility: Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)
state: Verona
city: Bergamo
country: Italy
facility: UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo
city: Bologna
country: Italy
facility: SSD di Oncologia Medica Addarii, Policlinico S. Orsola-Malpighi,
city: Bologna
country: Italy
facility: UOC di Oncologia. Azienda USL di Bologna, Ospedale Bellaria,
city: Bolzano
country: Italy
facility: Divisione di Oncologia Medica - Ospedale di Bolzano,
city: Brescia
country: Italy
facility: Breast Unit Spedali Civili di Brescia
city: Candiolo
country: Italy
facility: Investigational Clinical Oncology - INCOIRCCS-Fondazione del Piemonte per l'Oncologia (FPO)
city: Cremona
country: Italy
facility: Chirurgia generale ad indirizzo senologico-Breast Unit Azienda Istituti Ospitalieri di Cremona
city: Genova
country: Italy
facility: Dipartimento di Medicina Interna e Specialità Mediche (DI.M.I.)-Università di Genova Clinica di Medicina Interna ad indirizzo oncologico
city: Meldola (FC)
country: Italy
facility: Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola
city: Modena
country: Italy
facility: Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto. Policlinico di Modena
city: Monza
country: Italy
facility: SC di Oncologia Medica, A.O. San Gerardo
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica
city: Piacenza
country: Italy
facility: Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza
city: Reggio Emilia
country: Italy
facility: Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova
city: Rimini
country: Italy
facility: UO di Oncologia. Azienda USL di Rimini
city: Sassuolo
country: Italy
facility: Day Hospital, Ospedale di Sassuolo
city: Trento
country: Italy
facility: U.O. di Oncologia Medica PO "S. Chiara"
city: Verona
country: Italy
facility: Oncologia Medica Az. Ospedaliera di Verona
Study officials:
References: