Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in HER2+ Breast Cancer Patients
- Conditions
- Cancer, Breast
- Interventions
- Registration Number
- NCT03144947
- Lead Sponsor
- 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)
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 65
- 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.
- 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. -
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A Trastuzumab IV 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 B Trastuzumab SC 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 B Pertuzumab 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 A Pertuzumab 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 A Docetaxel 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 B Docetaxel 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
- Primary Outcome Measures
Name Time Method Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph) 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
Name Time Method HRQOL during study treatment based on FACT-B at baseline, and 6 months after last patient in mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.
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 Complete pathological response rate by treatment arm 6 months 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 5-year disease-free survival by treatment arm between treatment arms 5 years
Trial Locations
- Locations (21)
UO di Oncologia Ematologia, Azienda Ospedaliero Universitaria di Ferrara
🇮🇹Cona, Ferrara, Italy
Oncologia Medica, Ospedale Sacro Cuore - Don Calabria - Negrar (VR)
🇮🇹Negrar, Verona, Italy
UOC di Oncologia. Azienda USL di Bologna, Ospedale Bellaria,
🇮🇹Bologna, Italy
Oncologia Medica, IRST. Istituto Scientifico Romagnolo per lo studio e la cura dei Tumori, IRCCS di Meldola
🇮🇹Meldola (FC), 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
UOC Oncologia Medica, Azienda ULSS21 di Legnago
🇮🇹Legnago, Verona, 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
UOC Oncologia-A.O. PAPA GIOVANNI XXIII Bergamo
🇮🇹Bergamo, Italy
SSD di Oncologia Medica Addarii, Policlinico S. Orsola-Malpighi,
🇮🇹Bologna, Italy
Divisione di Oncologia Medica - Ospedale di Bolzano,
🇮🇹Bolzano, 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
Oncologia Medica Az. Ospedaliera di Verona
🇮🇹Verona, Italy