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

Cancer, Breast Clinical Trial

— 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03144947
• Other study ID #: GOIRC-01-2016
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 29, 2016
• Est. completion date: November 2021

Study information

• Verified date: October 2020
• Source: Gruppo Oncologico Italiano di Ricerca Clinica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 65
• Est. completion date: November 2021
• Est. primary completion date: March 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. -

Related Conditions & MeSH terms

• Breast Neoplasms
• Cancer, Breast

Intervention

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

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.

Locations

Country	Name	City	State
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	UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara	Cona	Ferrara
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	UOC Oncologia Medica, Azienda ULSS21 di Legnago	Legnago	Verona
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	Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)	Negrar	Verona
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

Sponsors (8)

Lead Sponsor

Collaborator

Gruppo Oncologico Italiano di Ricerca Clinica

Arithmos srl, Clirest s.r.l., Mipharm SpA, Temas srl, 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

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	HRQOL during study treatment based on FACT-B	mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.	at baseline, and 6 months after last patient in
Secondary	Complete pathological response rate by treatment arm		6 months after last patient in
Secondary	5-year disease-free survival by treatment arm between treatment arms		5 years