Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in HER2+ Breast Cancer Patients

NCT ID: NCT03144947

Last Updated: 2020-10-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-29
• Study Completion Date: 2021-11-30

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.

Conditions

Cancer, Breast

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Trastuzumab IV

Intervention Type: BIOLOGICAL

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.

Pertuzumab

Intervention Type: BIOLOGICAL

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

Docetaxel

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Trastuzumab SC

Intervention Type: BIOLOGICAL

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.

Pertuzumab

Intervention Type: BIOLOGICAL

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

Docetaxel

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Pertuzumab

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Other Intervention Names

Herceptin-150 mg; Herceptin-600 mg/5 mL; PerJeta 420 mg; Docetaxel 20 MG/ML

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. -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit

UNKNOWN

Sponsor Role: collaborator

University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology

UNKNOWN

Sponsor Role: collaborator

University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione

UNKNOWN

Sponsor Role: collaborator

Clirest s.r.l.

OTHER

Sponsor Role: collaborator

Mipharm SpA

UNKNOWN

Sponsor Role: collaborator

Arithmos srl

UNKNOWN

Sponsor Role: collaborator

Temas srl

UNKNOWN

Sponsor Role: collaborator

Gruppo Oncologico Italiano di Ricerca Clinica

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara

Cona, Ferrara, Italy

UOC Oncologia Medica, Azienda ULSS21 di Legnago

Legnago, Verona, Italy

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

Negrar, Verona, Italy

UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo

Bergamo, , Italy

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

Bologna, , Italy

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

Bologna, , Italy

Divisione di Oncologia Medica - Ospedale di Bolzano,

Bolzano, , Italy

Breast Unit Spedali Civili di Brescia

Brescia, , Italy

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

Candiolo, , Italy

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

Cremona, , Italy

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

Genova, , Italy

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

Meldola (FC), , Italy

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

Modena, , Italy

SC di Oncologia Medica, A.O. San Gerardo

Monza, , Italy

Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica

Parma, , Italy

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

Piacenza, , Italy

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

Reggio Emilia, , Italy

UO di Oncologia. Azienda USL di Rimini

Rimini, , Italy

Day Hospital, Ospedale di Sassuolo

Sassuolo, , Italy

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

Trento, , Italy

Oncologia Medica Az. Ospedaliera di Verona

Verona, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 38016718 (View on PubMed)

Other Identifiers

GOIRC-01-2016

Identifier Type: -

Identifier Source: org_study_id