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Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in Patients With HER2-positive Breast Cancer (IMMUN-HER)

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ClinicalTrials.gov Identifier: NCT03144947
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : February 27, 2019
Sponsor:
Collaborators:
University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit
University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology
University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione
Clirest s.r.l.
Mipharm SpA
Arithmos srl
Temas srl
Information provided by (Responsible Party):
Gruppo Oncologico Italiano di Ricerca Clinica

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)

Condition or disease Intervention/treatment Phase
Cancer, Breast Biological: Trastuzumab IV Biological: Trastuzumab SC Biological: Pertuzumab Drug: Docetaxel Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Other
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)
Actual Study Start Date : November 29, 2016
Estimated Primary Completion Date : March 15, 2019
Estimated Study Completion Date : November 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A

Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

After surgery, study patients will receive trastuzumab IV x 14 cycles

Biological: Trastuzumab IV

Pre-randomization phase:

FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2; cyclophosphamide 500 mg/m2) x 3 cycles

Post-randomization phase:

Group A: Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

*The dose of docetaxel may be escalated to 100 mg/m 2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated. After surgery, study patients will receive trastuzumab x 14 cycles using the same formulation (SC or IV) of the preoperative phase.

Other Name: Herceptin-150 mg

Biological: Pertuzumab
pertuzumab IV (840 mg loading dose, followed by 420 mg) weeks for 4 cycles (both arms)
Other Name: PerJeta 420 mg

Drug: Docetaxel
docetaxel (75 mg/m2), every 3 weeks for 4 cycles (both arms). The dose of docetaxel may be escalated to 100 mg/m2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated.
Other Name: Docetaxel 20 MG/ML

Experimental: Group B
Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles. After surgery, study patients will receive trastuzumab SC x 14 cycles
Biological: Trastuzumab SC

Pre-randomization phase:

FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2;

Group B: Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

*The dose of docetaxel may be escalated to 100 mg/m 2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated. After surgery, study patients will receive trastuzumab x 14 cycles using the same formulation (SC or IV) of the preoperative phase.

Other Name: Herceptin-600 mg/5 mL

Biological: Pertuzumab
pertuzumab IV (840 mg loading dose, followed by 420 mg) weeks for 4 cycles (both arms)
Other Name: PerJeta 420 mg

Drug: Docetaxel
docetaxel (75 mg/m2), every 3 weeks for 4 cycles (both arms). The dose of docetaxel may be escalated to 100 mg/m2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated.
Other Name: Docetaxel 20 MG/ML




Primary Outcome Measures :
  1. Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph) [ Time Frame: 6 months after last patient in ]
    stromal lymphocytes will be scored quantitatively on H&E stained whole-tumor slides as a continuous variable expressed as stromal percentage area within the tumor boundaries. For tumors with heterogeneous TILs, median values will be calculated from multiple counts from different tumor areas. Intra-epithelial TILs will also be recorded as well as tertiary lymphoid structures. Tumor regression will be scored based on recommended criteria.


Secondary Outcome Measures :
  1. Associations between biomarkers (TIL, Tumor specific lymphocyte cell activity (TLA), and Fc-gamma-R polymorphisms) and between each biomarker with clinical outcome variables. [ Time Frame: at baseline, 6 months and 5 years after last patient in ]
  2. 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) [ Time Frame: 3.5 years ]
  3. HRQOL during study treatment based on FACT-B [ Time Frame: at baseline, and 6 months after last patient in ]
    mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.

  4. Complete pathological response rate by treatment arm [ Time Frame: 6 months after last patient in ]
  5. 5-year disease-free survival by treatment arm between treatment arms [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03144947


Locations
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Italy
UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara Not yet recruiting
Cona, Ferrara, Italy, 44124
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Antonio Frassoldati, MD         
UOC Oncologia Medica, Azienda ULSS21 di Legnago Not yet recruiting
Legnago, Verona, Italy, 37045
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Andrea Bonetti, MD         
Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR) Recruiting
Negrar, Verona, Italy, 37024
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Stefania Gori, MD         
UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo Recruiting
Bergamo, Italy, 24127
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Alberto Zambelli, MD         
SSD di Oncologia Medica Addarii, Policlinico S. Orsola-Malpighi, Not yet recruiting
Bologna, Italy, 40138
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Claudio Zamagni, MD         
UOC di Oncologia. Azienda USL di Bologna, Ospedale Bellaria, Not yet recruiting
Bologna, Italy, 40139
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Alba Brandes, MD         
Divisione di Oncologia Medica - Ospedale di Bolzano, Not yet recruiting
Bolzano, Italy, 39100
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Claudio Graiff, MD         
Breast Unit Spedali Civili di Brescia Not yet recruiting
Brescia, Italy
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Edda Simoncini, MD         
Investigational Clinical Oncology - INCOIRCCS-Fondazione del Piemonte per l'Oncologia (FPO) Not yet recruiting
Candiolo (TO), Italy, 10060
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Filippo Montemurro, DM         
Chirurgia generale ad indirizzo senologico-Breast Unit Azienda Istituti Ospitalieri di Cremona Not yet recruiting
Cremona, Italy, 26100
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Daniele Generali, MD         
Dipartimento di Medicina Interna e Specialità Mediche (DI.M.I.)-Università di Genova Clinica di Medicina Interna ad indirizzo oncologico Not yet recruiting
Genova, Italy, 16132
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Alberto Ballestrieri, MD         
Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola Not yet recruiting
Meldola (FC), Italy, 47014
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Andrea Rocca, MD         
Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto. Policlinico di Modena Not yet recruiting
Modena, Italy, 41124
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Luca Moscetti, MD         
SC di Oncologia Medica, A.O. San Gerardo Not yet recruiting
Monza (MB), Italy, 20900
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Marina Cazzaniga, MD         
Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica Recruiting
Parma, Italy, 43100
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Antonio Musolino, MD         
Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza Recruiting
Piacenza, Italy, 29121
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Luigi Cavanna, MD         
Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova Recruiting
Reggio Emilia, Italy, 42123
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Giancarlo Bisagni, MD         
UO di Oncologia. Azienda USL di Rimini Recruiting
Rimini, Italy, 47923
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Lorenzo Gianni, MD         
Day Hospital, Ospedale di Sassuolo Not yet recruiting
Sassuolo (MO), Italy, 41049
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Giovanni Partesotti, MD         
U.O. di Oncologia Medica PO "S. Chiara" Not yet recruiting
Trento, Italy, 38122
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Antonella Ferro, MD         
Oncologia Medica Az. Ospedaliera di Verona Recruiting
Verona, Italy, 37126
Contact: Todeschini       infogoirc@libero.it   
Principal Investigator: Emilio Bria, MD         
Sponsors and Collaborators
Gruppo Oncologico Italiano di Ricerca Clinica
University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit
University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology
University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione
Clirest s.r.l.
Mipharm SpA
Arithmos srl
Temas srl

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Responsible Party: Gruppo Oncologico Italiano di Ricerca Clinica
ClinicalTrials.gov Identifier: NCT03144947     History of Changes
Other Study ID Numbers: GOIRC-01-2016
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Pertuzumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological