Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy.

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT03161353
• Date of registration: 15/05/2017
• Prospective Registration: Yes
• Primary sponsor: MedSIR
• Public title: Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy. PHERGain
• Scientific title: Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive (Human Epidermal Receptor) Breast Cancer: FDG-PET Response-adapted Strategy. The PHERGain Study
• Date of first enrolment: June 26, 2017
• Target sample size: 377
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03161353
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Belgium, France, Germany, Italy, Portugal, Spain, United Kingdom

Contacts

• Name: Antonio Llombart, MD
• Affiliation: Hospital Arnau de Vilanova

Key inclusion & exclusion criteria

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) (breast cancer TNM classification)

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 standarized uptake value (SUVmax: maximum standarized uptake value) =1.5 x
SUVmean (mean standarized uptake value) liver + 2 SD (standard deviation.

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 2018 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.

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 (TNM breast cancer classification)

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 (metastases) 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 arrythmias 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 conditions 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.

LINGain sub-study: The LINGAIN project intends to include a total of 126 blood samples from
PHERGain trial, as follows:

105 from patients treated with trastuzumab and pertuzumab ± endocrine therapy (according to
HR status); 21 from patients treated with trastuzumab and pertuzumab + carboplatin and
docetaxel.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Docetaxel

Drug: Carboplatin

Drug: Herceptin

Drug: Tamoxifen

Drug: Letrozole

Drug: Perjeta

Primary Outcome(s)

Evaluate the rate of pCR [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

3-year iDFS rate [Time Frame: After 3 years (36 months)]

Secondary Outcome(s)

18F-FDG PET/CT response rate (18F-FDG: 18F-fluorodeoxyglucose) [Time Frame: After cycle 2 (each cycle 21 days- After 42 days approximately)]

MRI response rate [Time Frame: After two cycles of neoadjuvant therapy, and prior to surgery (each cycle 21 days)]

Other 18FDG PET quantification parameters [Time Frame: After cycle 2 (each cycle 21 days- After 42 days approximately)]

3,5 and 7-year DDFS (DDFS:Distant disease-free survival) [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

Optimal 18F-FDG PET/CT cut-off for pCR [Time Frame: After cycle 2 (each cycle 21 days-After 42 days approximately)]

pCR rates in the breast and axilla [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

Health-related quality of life [Time Frame: Baseline, cycle 3 (after 63 days approximately), before surgery and end of study through study completion (after cycle 18- after 12 months approximately)]

3, 5 and 7-year DFS (DFS:Disease-free survival) [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

3, 5, and 7-year iDFS [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

pCR rates in the breast and axilla (ypTO/isN0) [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

Rate of breast conserving surgery [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

PFS (cohort C) (PFS: Progression-free survival) [Time Frame: Until progression or death, assessed up to approximately 84 months]

pCR rates in the breast (ypT0/is) [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

3, 5 and 7-year (OS: overall survival) [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

To assess 3, 5, and 7-year adapted iDFS, DDFS, and DFS [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

RCB score (residual cancer burden) [Time Frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)]

3, 5, and 7-year EFS [Time Frame: After 3, 5 and 7 years (After 36, 60 and 80 months)]

Adverse events [Time Frame: Until progression or death, assessed up to approximately 84 months]

Secondary ID(s)

2016-002676-27

MedOPP096

Source(s) of Monetary Support

Please refer to primary and secondary sponsors