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

Primary Purpose

Breast Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Perjeta
Herceptin
Docetaxel
Carboplatin
Letrozole
Tamoxifen
Sponsored by
MedSIR
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

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

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.

Sites / Locations

  • Institute Jules Bordet
  • CLCC d'Auvergne. Centre Jean Perrin.
  • Institute de Cancerologie de Laurraine
  • Groupe Hospitalier Diaconesses
  • Hopital Tenon
  • Hospital Georges Pompidou
  • Centre Paul Strauss
  • Institut Claudius Régaud
  • Kliniken Essen Mitte
  • Klinikum der Med. Fakultät Halle
  • National center for tumor disease NCT
  • Städtisches Klinikum "St. Georg" Leipzig
  • Hämatologisch-Onkologische Schwerpunktpraxis
  • Clinical of Nuclear Medicine Technical University Munich
  • Ospedale Maggiore Bologna
  • Ospedale Antonio Perrino
  • Istituto Ospedalieri di Cremona
  • Ospedale Mantova
  • Istituto Europeo di Oncologia
  • Ospedale San Gerardo
  • Ospedale Guglielmo de Saliceto
  • Hospital Senhora da Oliveira
  • Hospital Beatriz Angelo
  • Hospital da Luz
  • Hospital Fernando Fonseca
  • Centro Hospitalar Sao Joao
  • Hospital do Santo Antonio
  • Centro Hospitalaer de Tras-os-Montes e Alto Douro
  • ICO Badalona
  • ICO l'Hospitalet
  • Hospital Provincial de Castellón
  • Hospital de Jaén
  • Hospital Universitario Virgen de la Victoria
  • Hospital San Joan de Reus
  • Hospital Universitario A Coruña
  • Hospital Vall D'Hebrón
  • Hospital Clínic i Provincial de Barcelona
  • Hospital Universitario de Burgos
  • Hospital Reina Sofía
  • ICO Girona
  • Hospital Arnau de Vilanova
  • Hospital La Paz
  • Hospital Ramón y Cajal
  • CHUS Santiago de Compostela
  • Hospital Universitario Virgen del Rocío
  • Hospital Arnau de Vilanova
  • Hospital Clínic Universitari de Valencia
  • Hospital Dr Peset
  • Hospital General Universitari de Valencia
  • Hospital Universitari i Politecnic La Fe
  • Instituto Valenciano de Oncologia
  • Hospital Lozano Blesa
  • Hospital Universitario Miquel Servet
  • Barts Cancer Institute
  • The Christie NHS Foundation Trust
  • Royal Cornwall Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort A

Cohort B

Cohort C

Arm Description

Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".

Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".

cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery.

Outcomes

Primary Outcome Measures

Evaluate the rate of pCR
evaluate the rate of pCR as defined by the absence of invasive disease in the breast and axilla (ypT0/isN0) at the time of surgery achieved with the combination of trastuzumab and pertuzumab (± endocrine therapy) as exclusive neoadjuvant treatment in PET responders patients (cohort B/PET responders) [PET/CT positive predictive value (PPV) for a pCR among patients who are PET responders].
3-year iDFS rate
time from the first date of no disease (i.e., date of surgery) to invasive recurrence, new invasive disease, or death by any cause. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. The primary analysis will be to estimate 3-year iDFS rate in cohort B.

Secondary Outcome Measures

pCR rates in the breast and axilla (ypTO/isN0)
pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohort B/PET non-responders).
pCR rates in the breast (ypT0/is)
pCR rates in the breast (ypT0/is) (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
RCB score (residual cancer burden)
RCB score (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders
pCR rates in the breast and axilla
pCR rates in the breast and axilla (ypT0/isN0) according to HR status and tumor stage (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Rate of breast conserving surgery
Rate of breast conserving surgery (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
18F-FDG PET/CT response rate (18F-FDG: 18F-fluorodeoxyglucose)
18F-FDG PET/CT response rate (according to the adapted EORTC criteria) (cohort A; cohort B).
Optimal 18F-FDG PET/CT cut-off for pCR
Optimal 18F-FDG PET/CT cut-off for pCR (cohort A; cohort B).
Other 18FDG PET quantification parameters
Other 18F-FDG PET quantification parameters beside SUVmax for pCR (cohort A; cohort B). We will consider alternative measures to SUVmax in order to improve the ability to predict pCR; The best predictive parameter will be selected by means of logistic regressions models. For all tests, we will use two sided p-values with alpha ≤ 0.05 level of significance. The p-values emerging from these analyses will not be interpreted in a confirmative sense; they will be considered of descriptive nature only.
MRI response rate
MRI response rate [according to the Response Criteria in Solid Tumors (RECIST) criteria version 1.1] (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Health-related quality of life
Health-related quality of life (EORTC QLQ-C30- quality of life questionnaire and EORTC QLQ-BR23 quality of life questionnaires) (cohort A; cohort B; cohort C).All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/quality of life scale, and six single itemsThe QLQ-BR23 (quality of life questionnaire) breast cancer module is meant for use among patients varying in disease stage and treatment modality.The scoring approach for the QLQ-BR23 (quality of life questionnaire) is identical in principle to that for the function and symptom scales/single items of the QLQ-C30.
3-year iDFS (cohort A).
3-year iDFS (cohort A).
3-year DDFS (cohort A; cohort B) (DDFS:Distant disease-free survival)
3-year DDFS (cohort A; cohort B).
3-year DFS (cohort A; cohort B) (DFS:Disease-free survival)
3-year DFS (cohort A; cohort B).
OS (cohort A; cohort B; cohort C) (OS: overall survival)
OS (cohort A; cohort B; cohort C).
PFS (cohort C) (PFS: Progression-free survival)
PFS (cohort C).

Full Information

First Posted
May 15, 2017
Last Updated
January 18, 2023
Sponsor
MedSIR
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1. Study Identification

Unique Protocol Identification Number
NCT03161353
Brief Title
Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive Breast Cancer: FDG-PET Response-adapted Strategy.
Acronym
PHERGain
Official Title
Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive (Human Epidermal Receptor) Breast Cancer: FDG-PET Response-adapted Strategy. The PHERGain Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 26, 2017 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedSIR

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study assess the early metabolic effects of neoadjuvant treatment with trastuzumab and pertuzumab (± endocrine therapy) on the primary tumor and axillary lymph nodes and their predictive value for pathologic complete response (pCR) in the breast and axilla. And also assess 3-year invasive disease-free survival (iDFS) in patients with HER2-positive (HER: human epidermal receptor) breast cancer treated with neoadjuvant trastuzumab and pertuzumab (± endocrine therapy) using a FDG-PET response-adapted strategy.
Detailed Description
Investigational Medicinal Products (IMPs) will be trastuzumab and pertuzumab, carboplatin, and docetaxel, as well as all endocrine therapy drugs to be administered according to HR status (hormone receptor). For cohort C, trastuzumab SC (subcutaneous) and pertuzumab IV will be IMPs until a maximum of 18 cycles. Patients will be randomly assigned in a 1:4 ratio, with a randomization stratified by HR status to receive trastuzumab and pertuzumab with docetaxel and carboplatin (cohort A) or trastuzumab and pertuzumab ± endocrine therapy according to HR status (cohort B). A F-FDG PET/CT will be performed at baseline (total body) and after 2 cycles of neoadjuvant therapy. Central review of F-FDG PET/CT will be mandatory. Patients allocated into cohort A will continue with the same treatment for a total of six cycles regardless of 18F-FDG PET/CT results. Patients enrolled into cohort B showing at least 40% reduction of the SUVmax of F-FDG PET/CT respect to baseline (PET responders) will continue with the same treatment for a total of 8 cycles. PET-non responders patients will also receive neoadjuvant chemotherapy based on six cycles of docetaxel and carboplatin concurrently with trastuzumab and pertuzumab for all cycles. Following surgery, cohort B/PET responders patients who do not achieve a pCR will additionally receive six cycles of docetaxel and carboplatin concurrently with trastuzumab and pertuzumab for all cycles. Moreover, all patients from cohorts A/B must complete 18 cycles of trastuzumab and pertuzumab, along with adjuvant endocrine therapy and radiotherapy according to HR status (hormone receptor) and institutional practices, respectively. An additional exploratory cohort (cohort C) will include patients with evidence of subclinic M1 at baseline 18F-FDG PET/CT, but not previously detected by routine clinical assessment. These patients will receive trastuzumab and pertuzumab with docetaxel and carboplatin for a total of six cycles. After first six cycles, these patients will receive trastuzumab and pertuzumab ± endocrine.therapy according to HR status for at least 12 additional cycles after surgery (only if surgery is performed). According to institutional practices, it will be allowed to continue treatment with trastuzumab and pertuzumab, along endocrine therapy on the basis of HR status, as maintenance therapy until disease progression or unacceptable toxicity. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study" : Hospital General de Valencia, Hospital Clínico Universitario de Valencia, IVO, Hospital La Fe and Hospital Arnau de Vilanova.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This randomized, open-label phase II study will assess the efficacy of the combination of trastuzumab and pertuzumab, ± endocrine therapy according to HR (hormone receptor) status, as exclusive neoadjuvant and adjuvant treatment in patients with HER2-positive breast cancer through a FDG-PET response-adapted strategy.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
377 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A
Arm Type
Experimental
Arm Description
Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel (during 4 cycles): PET responders or not responders after surgery: Continue with Perjeta+Herceptin+ Endocrine therapy (tamoxifen or letrozole) during 12 cycles A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
Cohorts A/B if there is no evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening. Interventional: Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) during 2 cycles. PET responders: Perjeta+Herceptin+Endocrine therapy during 6 cycles. -Complete response: continue with Perjeta+Herceptin+ Endocrine therapy during 10 cycles -Non-complete response: Perjeta+Herceptin+ Carboplatin+ Docetaxel during 6 cycles and Perjeta+Herceptin+Endocrine therapy during 4 cycles. PET non-responders: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients with or without complete response will continue with Perjeta+Herceptin+Endocrine therapy during 10 cycles. A sub-set of 42 patients (35 patients from cohort A and 7 patients from cohort B) from 5 sites in Spain are participating in the LINGain sub-study "Prospective evaluation of predictive/prognostic immunogenicity biomarkers for target therapy in HER2-positive early breast cancer within the PHERGain study".
Arm Title
Cohort C
Arm Type
Experimental
Arm Description
cohorts C if there is evidence of subclinic M1 assessed by 18F-FDG PET/CT at screening Interventional: Perjeta+Herceptin+Carboplatin+Docetaxel during 6 cycles. Patients will continue with Perjeta+Herceptin+Endocrine therapy (tamoxifen or letrozole) after surgery or no surgery.
Intervention Type
Drug
Intervention Name(s)
Perjeta
Other Intervention Name(s)
Pertuzumab
Intervention Description
All patients will receive Perjeta® as an IV infusion on Day 1 of the first treatment cycle as a loading dose of 840 mg, followed by 420 mg on Day 1 of each subsequent 3-week cycle. Perjeta® IV should be administered 60 minutes after the end of Herceptin® SC (subcutaneous) administration. An observation period of 30-60 minutes is recommended after each Perjeta® infusion.
Intervention Type
Drug
Intervention Name(s)
Herceptin
Other Intervention Name(s)
Trastuzumab
Intervention Description
All patients will receive a fixed dose of 600 mg, irrespective of the patient's weight, will be administered throughout the treatment phase. All doses of Herceptin® SC will be administered as an SC injection into the thigh by a trained health care professional over a period of 2-5 minutes. No loading dose is required with Herceptin® SC.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Docetaxel will be administered in line with the respective product information and/or recognized clinical practice guidelines. It will be administered after Herceptin® SC, Perjeta® IV, and carboplatin
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin will be administered in line with the respective product information and/or recognized clinical practice guidelines. It will be administered after Herceptin® SC and Perjeta® IV.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
Postmenopausal women will receive letrozole 2.5 mg tablet orally once daily beginning on Day 1 and continuing through Day 21 of a 21-day cycle as neoadjuvant therapy.
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
Premenopausal women will receive tamoxifen 20 mg tablet orally once daily beginning on Day 1 and continuing through Day 21 of a 21-day cycle as neoadjuvant therapy. Male patients will receive tamoxifen 20 mg tablet orally once daily beginning on Day 1 and continuing through Day 21 of a 21-day cycle as neoadjuvant therapy.
Primary Outcome Measure Information:
Title
Evaluate the rate of pCR
Description
evaluate the rate of pCR as defined by the absence of invasive disease in the breast and axilla (ypT0/isN0) at the time of surgery achieved with the combination of trastuzumab and pertuzumab (± endocrine therapy) as exclusive neoadjuvant treatment in PET responders patients (cohort B/PET responders) [PET/CT positive predictive value (PPV) for a pCR among patients who are PET responders].
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
3-year iDFS rate
Description
time from the first date of no disease (i.e., date of surgery) to invasive recurrence, new invasive disease, or death by any cause. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. The primary analysis will be to estimate 3-year iDFS rate in cohort B.
Time Frame
After 3 years (36 months)
Secondary Outcome Measure Information:
Title
pCR rates in the breast and axilla (ypTO/isN0)
Description
pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohort B/PET non-responders).
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
pCR rates in the breast (ypT0/is)
Description
pCR rates in the breast (ypT0/is) (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
RCB score (residual cancer burden)
Description
RCB score (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
pCR rates in the breast and axilla
Description
pCR rates in the breast and axilla (ypT0/isN0) according to HR status and tumor stage (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
Rate of breast conserving surgery
Description
Rate of breast conserving surgery (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Time Frame
After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)
Title
18F-FDG PET/CT response rate (18F-FDG: 18F-fluorodeoxyglucose)
Description
18F-FDG PET/CT response rate (according to the adapted EORTC criteria) (cohort A; cohort B).
Time Frame
After cycle 2 (each cycle 21 days- After 42 days approximately)
Title
Optimal 18F-FDG PET/CT cut-off for pCR
Description
Optimal 18F-FDG PET/CT cut-off for pCR (cohort A; cohort B).
Time Frame
After cycle 2 (each cycle 21 days-After 42 days approximately)
Title
Other 18FDG PET quantification parameters
Description
Other 18F-FDG PET quantification parameters beside SUVmax for pCR (cohort A; cohort B). We will consider alternative measures to SUVmax in order to improve the ability to predict pCR; The best predictive parameter will be selected by means of logistic regressions models. For all tests, we will use two sided p-values with alpha ≤ 0.05 level of significance. The p-values emerging from these analyses will not be interpreted in a confirmative sense; they will be considered of descriptive nature only.
Time Frame
After cycle 2 (each cycle 21 days- After 42 days approximately)
Title
MRI response rate
Description
MRI response rate [according to the Response Criteria in Solid Tumors (RECIST) criteria version 1.1] (cohort A; cohort B; cohort B/PET responders; cohort B/PET non-responders).
Time Frame
After two cycles of neoadjuvant therapy, and prior to surgery (each cycle 21 days)
Title
Health-related quality of life
Description
Health-related quality of life (EORTC QLQ-C30- quality of life questionnaire and EORTC QLQ-BR23 quality of life questionnaires) (cohort A; cohort B; cohort C).All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. The EORTC QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/quality of life scale, and six single itemsThe QLQ-BR23 (quality of life questionnaire) breast cancer module is meant for use among patients varying in disease stage and treatment modality.The scoring approach for the QLQ-BR23 (quality of life questionnaire) is identical in principle to that for the function and symptom scales/single items of the QLQ-C30.
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)
Title
3-year iDFS (cohort A).
Description
3-year iDFS (cohort A).
Time Frame
After 3 years (After 36 months)
Title
3-year DDFS (cohort A; cohort B) (DDFS:Distant disease-free survival)
Description
3-year DDFS (cohort A; cohort B).
Time Frame
After 3 years (After 36 months)
Title
3-year DFS (cohort A; cohort B) (DFS:Disease-free survival)
Description
3-year DFS (cohort A; cohort B).
Time Frame
After 3 years (After 36 months)
Title
OS (cohort A; cohort B; cohort C) (OS: overall survival)
Description
OS (cohort A; cohort B; cohort C).
Time Frame
After 3 years (After 36 months)
Title
PFS (cohort C) (PFS: Progression-free survival)
Description
PFS (cohort C).
Time Frame
After 3 years (After 36 months)
Other Pre-specified Outcome Measures:
Title
LINGain sub-study: analyze the variation of peripheral γδ T cells in blood samples
Description
• To analyse the variation of peripheral γδ T cells in blood samples from patients with HER2-positive early breast cancer in neoadjuvant treatment with trastuzumab and pertuzumab (± endocrine therapy) at 6 weeks after start of treatment (end of the 2nd cycle of treatment) respect to the baseline.
Time Frame
Screening, end of cycle 1 and end of cycle 2 (each cycle is 21 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent prior to beginning specific protocol procedures. Female or male patients ≥ 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Histologically proven invasive breast cancer. Operable breast cancer (cT1-3 and/or cN0-2 tumors) (breast cancer TNM classification) 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: Histological confirmation of at least two lesions. All tumors must be HER2-positive. 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: Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. cT4 and/or cN3 tumors (TNM breast cancer classification) Bilateral breast cancer. 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. Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances. 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. Left ventricular ejection fraction (LVEF) below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO). Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment. 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]. Active uncontrolled infection at the time of enrollment. Current known infection with HIV, hepatitis B virus, or hepatitis C virus. Patients with pulmonary disease requiring continuous oxygen therapy. Previous history of bleeding diathesis. Patient is currently receiving anti-coagulant therapy, chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed). 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. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the investigator´s judgment, contraindicate her participation in the clinical study. Concurrent participation in other clinical trial, except other translational studies. History of receiving any investigational treatment within 28 days prior to randomization. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Llombart, MD
Organizational Affiliation
Hospital Arnau de Vilanova
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute Jules Bordet
City
Bruxelles
Country
Belgium
Facility Name
CLCC d'Auvergne. Centre Jean Perrin.
City
Clermont-Ferrand
Country
France
Facility Name
Institute de Cancerologie de Laurraine
City
Nancy
Country
France
Facility Name
Groupe Hospitalier Diaconesses
City
Paris
Country
France
Facility Name
Hopital Tenon
City
Paris
Country
France
Facility Name
Hospital Georges Pompidou
City
Paris
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
Country
France
Facility Name
Institut Claudius Régaud
City
Toulouse
Country
France
Facility Name
Kliniken Essen Mitte
City
Essen
Country
Germany
Facility Name
Klinikum der Med. Fakultät Halle
City
Halle
Country
Germany
Facility Name
National center for tumor disease NCT
City
Heidelberg
Country
Germany
Facility Name
Städtisches Klinikum "St. Georg" Leipzig
City
Leipzig
Country
Germany
Facility Name
Hämatologisch-Onkologische Schwerpunktpraxis
City
Munchen
Country
Germany
Facility Name
Clinical of Nuclear Medicine Technical University Munich
City
Munich
Country
Germany
Facility Name
Ospedale Maggiore Bologna
City
Bologna
Country
Italy
Facility Name
Ospedale Antonio Perrino
City
Brindisi
Country
Italy
Facility Name
Istituto Ospedalieri di Cremona
City
Cremona
Country
Italy
Facility Name
Ospedale Mantova
City
Mantova
Country
Italy
Facility Name
Istituto Europeo di Oncologia
City
Milan
Country
Italy
Facility Name
Ospedale San Gerardo
City
Monza
Country
Italy
Facility Name
Ospedale Guglielmo de Saliceto
City
Piacenza
Country
Italy
Facility Name
Hospital Senhora da Oliveira
City
Guimarães
Country
Portugal
Facility Name
Hospital Beatriz Angelo
City
Lisboa
Country
Portugal
Facility Name
Hospital da Luz
City
Lisboa
Country
Portugal
Facility Name
Hospital Fernando Fonseca
City
Lisboa
Country
Portugal
Facility Name
Centro Hospitalar Sao Joao
City
Oporto
Country
Portugal
Facility Name
Hospital do Santo Antonio
City
Oporto
Country
Portugal
Facility Name
Centro Hospitalaer de Tras-os-Montes e Alto Douro
City
Vila Real
Country
Portugal
Facility Name
ICO Badalona
City
Badalona
State/Province
Barcelona
Country
Spain
Facility Name
ICO l'Hospitalet
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08007
Country
Spain
Facility Name
Hospital Provincial de Castellón
City
Castello
State/Province
Castelló
Country
Spain
Facility Name
Hospital de Jaén
City
Jaen
State/Province
Jaén
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria
City
Malaga
State/Province
Málaga
Country
Spain
Facility Name
Hospital San Joan de Reus
City
Reus
State/Province
Tarragona
Country
Spain
Facility Name
Hospital Universitario A Coruña
City
A Coruna
Country
Spain
Facility Name
Hospital Vall D'Hebrón
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínic i Provincial de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Burgos
City
Burgos
Country
Spain
Facility Name
Hospital Reina Sofía
City
Cordoba
Country
Spain
Facility Name
ICO Girona
City
Girona
Country
Spain
Facility Name
Hospital Arnau de Vilanova
City
Lleida
Country
Spain
Facility Name
Hospital La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
CHUS Santiago de Compostela
City
Santiago de Compostela
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
Country
Spain
Facility Name
Hospital Arnau de Vilanova
City
Valencia
Country
Spain
Facility Name
Hospital Clínic Universitari de Valencia
City
Valencia
Country
Spain
Facility Name
Hospital Dr Peset
City
Valencia
Country
Spain
Facility Name
Hospital General Universitari de Valencia
City
Valencia
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe
City
Valencia
Country
Spain
Facility Name
Instituto Valenciano de Oncologia
City
Valencia
Country
Spain
Facility Name
Hospital Lozano Blesa
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Hospital Universitario Miquel Servet
City
Zaragoza
Country
Spain
Facility Name
Barts Cancer Institute
City
London
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36300423
Citation
Perez-Garcia JM, Gebhart G, Borrego MR, Schmid P, Marme F, Prat A, Dalenc F, Kerrou K, Colleoni M, Braga S, Malfettone A, Sampayo-Cordero M, Cortes J, Llombart-Cussac A. Trastuzumab and pertuzumab without chemotherapy in early-stage HER2+ breast cancer: a plain language summary of the PHERGain study. Future Oncol. 2022 Oct;18(33):3677-3688. doi: 10.2217/fon-2022-0663. Epub 2022 Oct 27.
Results Reference
derived
PubMed Identifier
34019819
Citation
Perez-Garcia JM, Gebhart G, Ruiz Borrego M, Stradella A, Bermejo B, Schmid P, Marme F, Escriva-de-Romani S, Calvo L, Ribelles N, Martinez N, Albacar C, Prat A, Dalenc F, Kerrou K, Colleoni M, Afonso N, Di Cosimo S, Sampayo-Cordero M, Malfettone A, Cortes J, Llombart-Cussac A; PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an 18F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):858-871. doi: 10.1016/S1470-2045(21)00122-4. Epub 2021 May 18.
Results Reference
derived

Learn more about this trial

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

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