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

Primary Purpose

Cancer, Breast

Status

Unknown status

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Trastuzumab IV

Trastuzumab SC

Pertuzumab

Docetaxel

About this trial

This is an interventional other trial for Cancer, Breast

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. -

Sites / Locations

UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara
UOC Oncologia Medica, Azienda ULSS21 di Legnago
Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)
UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo
SSD di Oncologia Medica Addarii, Policlinico S. Orsola-Malpighi,
UOC di Oncologia. Azienda USL di Bologna, Ospedale Bellaria,
Divisione di Oncologia Medica - Ospedale di Bolzano,
Breast Unit Spedali Civili di Brescia
Investigational Clinical Oncology - INCOIRCCS-Fondazione del Piemonte per l'Oncologia (FPO)
Chirurgia generale ad indirizzo senologico-Breast Unit Azienda Istituti Ospitalieri di Cremona
Dipartimento di Medicina Interna e Specialità Mediche (DI.M.I.)-Università di Genova Clinica di Medicina Interna ad indirizzo oncologico
Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola
Dipartimento di Scienze Mediche e Chirurgiche, Materno Infantili e dell'adulto. Policlinico di Modena
SC di Oncologia Medica, A.O. San Gerardo
Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica
Dipartimento di Oncologia e Ematologia, UO di Oncologia Medica Azienda USL di Piacenza
Struttura Complessa di OncologiaIRCCS- Istituto in Tecnologie Avanzate e Modelli Assistenziali in Oncologia Arcispedale Santa Maria Nuova
UO di Oncologia. Azienda USL di Rimini
Day Hospital, Ospedale di Sassuolo
U.O. di Oncologia Medica PO "S. Chiara"
Oncologia Medica Az. Ospedaliera di Verona

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group A

Group B

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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)

HRQOL during study treatment based on FACT-B

mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.

Complete pathological response rate by treatment arm

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

Full Information

NCT ID

NCT03144947

First Posted

April 7, 2017

Last Updated

October 12, 2020

Sponsor

Gruppo Oncologico Italiano di Ricerca Clinica

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

1. Study Identification

Unique Protocol Identification Number

NCT03144947

Brief Title

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

Acronym

IMMUN-HER

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Unknown status

Study Start Date

November 29, 2016 (Actual)

Primary Completion Date

March 15, 2021 (Anticipated)

Study Completion Date

November 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gruppo Oncologico Italiano di Ricerca Clinica

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer, Breast

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Experimental

Arm Description

Arm Title

Group B

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Trastuzumab IV

Other Intervention Name(s)

Herceptin-150 mg

Intervention Description

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

Intervention Name(s)

Trastuzumab SC

Other Intervention Name(s)

Herceptin-600 mg/5 mL

Intervention Description

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

Intervention Name(s)

Pertuzumab

Other Intervention Name(s)

PerJeta 420 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Docetaxel 20 MG/ML

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

6 months after last patient in

Secondary Outcome Measure Information:

Title

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

Title

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

Title

HRQOL during study treatment based on FACT-B

Description

mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.

Time Frame

at baseline, and 6 months after last patient in

Title

Complete pathological response rate by treatment arm

Time Frame

6 months after last patient in

Title

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

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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. -

Facility Information:

Facility Name

UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara

City

Cona

State/Province

Ferrara

ZIP/Postal Code

44124

Country

Italy

Facility Name

UOC Oncologia Medica, Azienda ULSS21 di Legnago

City

Legnago

State/Province

Verona

ZIP/Postal Code

37045

Country

Italy

Facility Name

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

City

Negrar

State/Province

Verona

ZIP/Postal Code

37024

Country

Italy

Facility Name

UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo

City

Bergamo

ZIP/Postal Code

24127

Country

Italy

Facility Name

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

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

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

City

Bologna

ZIP/Postal Code

40139

Country

Italy

Facility Name

Divisione di Oncologia Medica - Ospedale di Bolzano,

City

Bolzano

ZIP/Postal Code

39100

Country

Italy

Facility Name

Breast Unit Spedali Civili di Brescia

City

Brescia

Country

Italy

Facility Name

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

City

Candiolo

ZIP/Postal Code

10060

Country

Italy

Facility Name

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

City

Cremona

ZIP/Postal Code

26100

Country

Italy

Facility Name

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

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

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

City

Meldola (FC)

ZIP/Postal Code

47014

Country

Italy

Facility Name

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

City

Modena

ZIP/Postal Code

41124

Country

Italy

Facility Name

SC di Oncologia Medica, A.O. San Gerardo

City

Monza

ZIP/Postal Code

20900

Country

Italy

Facility Name

Azienda Ospedaliero-Universitaria di Parma, UOC di Oncologia Medica

City

Parma

ZIP/Postal Code

43100

Country

Italy

Facility Name

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

City

Piacenza

ZIP/Postal Code

29121

Country

Italy

Facility Name

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

City

Reggio Emilia

ZIP/Postal Code

42123

Country

Italy

Facility Name

UO di Oncologia. Azienda USL di Rimini

City

Rimini

ZIP/Postal Code

47923

Country

Italy

Facility Name

Day Hospital, Ospedale di Sassuolo

City

Sassuolo

ZIP/Postal Code

41049

Country

Italy

Facility Name

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

City

Trento

ZIP/Postal Code

38122

Country

Italy

Facility Name

Oncologia Medica Az. Ospedaliera di Verona

City

Verona

ZIP/Postal Code

37126

Country

Italy

12. IPD Sharing Statement

Learn more about this trial

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

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