Chemotherapy-free trastuzumab and pertuzumab in HER2-positive breast cancer after FDG-PET response-adapted strategy. The PHERGain study

Phase 1

Conditions: HER2-positive breast cancer
MedDRA version: 19.1Level: PTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002676-27-ES

Lead Sponsor: Medica Scientia Innovation Research (MedSIR)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 400

Inclusion Criteria

1)Written informed consent prior to beginning specific protocol procedures.
2)Female or male patients = 18 years of age.
3)Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4)Histologically proven invasive breast cancer.
5)Operable breast cancer (cT1-3 and/or cN0-2 tumors).
6)Tumor size larger than or equal to 1.5 centimeter (cm) in diameter by magnetic resonance imaging (MRI) or ultrasound with a significant 18F-FDG uptake defined as maximum standardized uptake value (SUVmax) =1.5 x SUVmean liver + 2 SD.
Multicentric/multifocal tumors will be allowed only if:
1. Histological confirmation of at least two lesions.
2. All tumors must be HER2-positive.
3. Largest lesion must be larger than or equal to 1.5 cm in diameter by MRI or ultrasound.
7)Centrally confirmed HER2-positive disease according to the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria.
8)Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry.

Patient has adequate bone marrow, liver, and renal function:

9)Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) = 1.5 x 109/L, platelet count = 100.0 x109/L, and hemoglobin = 10.0 g/dL (= 6.2 mmol/L).
10)Hepatic: total bilirubin = institutional upper limit of normal (ULN) (except for Gilbert’s syndrome); alkaline phosphatase (ALP) = 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) = 1.5 times ULN.
11)Renal: serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
12)Patient must be accessible for treatment and follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion Criteria

1)Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer.
2)cT4 and/or cN3 tumors.
3)Bilateral breast cancer.
4)Evidence of metastatic disease by routine clinical assessment ?chest x-ray, liver ultrasound, and bone scan; or computed tomography (CT) scan of thorax and abdomen and bone scan?, except patients with subclinic M1 at baseline only according to 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) that will be allowed to be included into Cohort C.
5)Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances.
6)History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma.
7)Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO).
8)Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment.
9)Clinically significant cardiovascular disease [stroke, unstable angina pectoris, or documented myocardial infarction within six months prior to study entry; history of documented congestive heart failure (CHF) (New York Heart Association II-III-IV); symptomatic pericarditis; documented cardiomyopathy; ventricular arrytmhias with the exception of benign premature ventricular contractions; conduction abnormality requiring a pacemaker; other arrhythmias not controlled with medication].
10)Active uncontrolled infection at the time of enrollment.
11)Current known infection with HIV, hepatitis B virus, or hepatitis C virus.
12)Patients with pulmonary disease requiring continuous oxygen therapy.
13)Previous history of bleeding diathesis.
14)Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed).
15)Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of need for major surgery within the course of the study treatment.
16)Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator´s judgment, contraindicate her participation in the clinical study.
17)Concurrent participation in other clinical trial, except other translational studies.
18)History of receiving any investigational treatment within 28 days prior to randomization.
19)Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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