NCT03144947

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)

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
65

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Nov 2016

Longer than P75 for phase_2

Geographic Reach
1 country

21 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 29, 2016

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 7, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 9, 2017

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2021

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2021

Completed
Last Updated

October 14, 2020

Status Verified

October 1, 2020

Enrollment Period

4.3 years

First QC Date

April 7, 2017

Last Update Submit

October 12, 2020

Conditions

Cancer, Breast

Outcome Measures

Primary Outcomes (1)

  • Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph)

    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.

    6 months after last patient in

Secondary Outcomes (5)

  • Associations between biomarkers (TIL, Tumor specific lymphocyte cell activity (TLA), and Fc-gamma-R polymorphisms) and between each biomarker with clinical outcome variables.

    at baseline, 6 months and 5 years after last patient in

  • 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)

    3.5 years

  • HRQOL during study treatment based on FACT-B

    at baseline, and 6 months after last patient in

  • Complete pathological response rate by treatment arm

    6 months after last patient in

  • 5-year disease-free survival by treatment arm between treatment arms

    5 years

Study Arms (2)

Group A

EXPERIMENTAL

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 IVBiological: PertuzumabDrug: Docetaxel

Group B

EXPERIMENTAL

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 SCBiological: PertuzumabDrug: Docetaxel

Interventions

Trastuzumab IVBIOLOGICAL

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.

Also known as: Herceptin-150 mg
Group A
Trastuzumab SCBIOLOGICAL

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.

Also known as: Herceptin-600 mg/5 mL
Group B
PertuzumabBIOLOGICAL

pertuzumab IV (840 mg loading dose, followed by 420 mg) weeks for 4 cycles (both arms)

Also known as: PerJeta 420 mg
Group AGroup B
DocetaxelDRUG

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.

Also known as: Docetaxel 20 MG/ML
Group AGroup B

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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. -

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara

Cona, Ferrara, 44124, Italy

Location

UOC Oncologia Medica, Azienda ULSS21 di Legnago

Legnago, Verona, 37045, Italy

Location

Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)

Negrar, Verona, 37024, Italy

Location

UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo

Bergamo, 24127, Italy

Location

SSD di Oncologia Medica Addarii, Policlinico S. Orsola-Malpighi,

Bologna, 40138, Italy

Location

UOC di Oncologia. Azienda USL di Bologna, Ospedale Bellaria,

Bologna, 40139, Italy

Location

Divisione di Oncologia Medica - Ospedale di Bolzano,

Bolzano, 39100, Italy

Location

Breast Unit Spedali Civili di Brescia

Brescia, Italy

Location

Investigational Clinical Oncology - INCOIRCCS-Fondazione del Piemonte per l'Oncologia (FPO)

Candiolo, 10060, Italy

Location

Chirurgia generale ad indirizzo senologico-Breast Unit Azienda Istituti Ospitalieri di Cremona

Cremona, 26100, Italy

Location

Dipartimento di Medicina Interna e Specialità Mediche (DI.M.I.)-Università di Genova Clinica di Medicina Interna ad indirizzo oncologico

Genova, 16132, Italy

Location

Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola

Meldola (FC), 47014, Italy

Location

Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto. Policlinico di Modena

Modena, 41124, Italy

Location

SC di Oncologia Medica, A.O. San Gerardo

Monza, 20900, Italy

Location

Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica

Parma, 43100, Italy

Location

Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza

Piacenza, 29121, Italy

Location

Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova

Reggio Emilia, 42123, Italy

Location

UO di Oncologia. Azienda USL di Rimini

Rimini, 47923, Italy

Location

Day Hospital, Ospedale di Sassuolo

Sassuolo, 41049, Italy

Location

U.O. di Oncologia Medica PO "S. Chiara"

Trento, 38122, Italy

Location

Oncologia Medica Az. Ospedaliera di Verona

Verona, 37126, Italy

Location

Related Publications (1)

  • Pellegrino B, Tommasi C, Serra O, Gori S, Cretella E, Ambroggi M, Frassoldati A, Bisagni G, Casarini C, Bria E, Carbognin L, Fiorio E, Mura A, Zamagni C, Gianni L, Zambelli A, Montemurro F, Tognetto M, Todeschini R, Missale G, Campanini N, Silini EM, Maglietta G, Musolino A. Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016). J Immunother Cancer. 2023 Nov 28;11(11):e007667. doi: 10.1136/jitc-2023-007667.

    PMID: 38016718DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumabDocetaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Model Details: Non comparative, multi-center, open-label, neoadjuvant, randomized study, the purpose of randomization is to reduce bias owing to patient selection into treatments groups.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 7, 2017

First Posted

May 9, 2017

Study Start

November 29, 2016

Primary Completion

March 15, 2021

Study Completion

November 1, 2021

Last Updated

October 14, 2020

Record last verified: 2020-10

Locations

IT(21)