AzTrials
AzTrials

Breast CancerPhase 2PHERGainNCT03161353

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

A Phase 2 study testing Perjeta, Herceptin and Docetaxel in people with Breast Cancer, run by MedSIR at 56 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Perjeta, Herceptin and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
377 participants
Where
56 sitesin 7 countries
Study dates
26 Jun 2017to 1 Nov 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 21Show fewer
  • 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.

Trial locations and contacts

56 sites in 7 countries.

56 sites in 7 countries

Spain25 sites

  • Hospital Universitario A Coruña

    A Coruña

  • ICO Badalona

    Badalona, Barcelona

  • Hospital Vall D'Hebrón

    Barcelona, 08035

  • Hospital Clínic i Provincial de Barcelona

    Barcelona

  • Hospital Universitario de Burgos

    Burgos

  • Hospital Provincial de Castellón

    Castelló, Castelló

  • Hospital Reina Sofía

    Córdoba

  • ICO Girona

    Girona

  • Hospital de Jaén

    Jaén, Jaén

  • ICO l'Hospitalet

    L'Hospitalet de Llobregat, Barcelona, 08007

  • Hospital Arnau de Vilanova

    Lleida

  • Hospital La Paz

    Madrid

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Universitario Virgen de la Victoria

    Málaga, Málaga

  • Hospital San Joan de Reus

    Reus, Tarragona

  • CHUS Santiago de Compostela

    Santiago de Compostela

  • Hospital Universitario Virgen del Rocío

    Seville

  • Hospital Arnau de Vilanova

    Valencia

  • Hospital Clínic Universitari de Valencia

    Valencia

  • Hospital Dr Peset

    Valencia

  • Hospital General Universitari de Valencia

    Valencia

  • Hospital Universitari i Politecnic La Fe

    Valencia

  • Instituto Valenciano de Oncologia

    Valencia

  • Hospital Lozano Blesa

    Zaragoza, 50009

  • Hospital Universitario Miquel Servet

    Zaragoza

Other trials in Spain

France7 sites

  • CLCC d'Auvergne. Centre Jean Perrin.

    Clermont-Ferrand

  • Institute de Cancerologie de Laurraine

    Nancy

  • Groupe Hospitalier Diaconesses

    Paris

  • Hopital Tenon

    Paris

  • Hospital Georges Pompidou

    Paris

  • Centre Paul Strauss

    Strasbourg

  • Institut Claudius Régaud

    Toulouse

Other trials in France

Italy7 sites

  • Ospedale Maggiore Bologna

    Bologna

  • Ospedale Antonio Perrino

    Brindisi

  • Istituto Ospedalieri di Cremona

    Cremona

  • Ospedale Mantova

    Mantua

  • Istituto Europeo di Oncologia

    Milan

  • Ospedale San Gerardo

    Monza

  • Ospedale Guglielmo de Saliceto

    Piacenza

Other trials in Italy

Portugal7 sites

  • Hospital Senhora da Oliveira

    Guimarães

  • Hospital Beatriz Angelo

    Lisbon

  • Hospital da Luz

    Lisbon

  • Hospital Fernando Fonseca

    Lisbon

  • Centro Hospitalar Sao Joao

    Porto

  • Hospital do Santo Antonio

    Porto

  • Centro Hospitalaer de Tras-os-Montes e Alto Douro

    Vila Real

Other trials in Portugal

Germany6 sites

  • Kliniken Essen Mitte

    Essen

  • Klinikum der Med. Fakultät Halle

    Halle

  • National center for tumor disease NCT

    Heidelberg

  • Städtisches Klinikum "St. Georg" Leipzig

    Leipzig

  • Hämatologisch-Onkologische Schwerpunktpraxis

    München

  • Clinical of Nuclear Medicine Technical University Munich

    Munich

Other trials in Germany

United Kingdom3 sites

  • Barts Cancer Institute

    London

  • The Christie NHS Foundation Trust

    Manchester

  • Royal Cornwall Hospital

    Truro

Other trials in United Kingdom

Belgium1 site

  • Institute Jules Bordet

    Brussels

Other trials in Belgium

About this study

Official title: Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive (Human Epidermal Receptor) Breast Cancer: FDG-PET Response-adapted Strategy. The PHERGain Study

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.

Read the 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.

Conditions
Breast Cancer
Being tested
Perjeta, Herceptin, Docetaxel, Carboplatin, Letrozole
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PerjetaDrug

    Also called Pertuzumab

    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.

  • HerceptinDrug

    Also called Trastuzumab

    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.

  • DocetaxelDrug

    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

  • CarboplatinDrug

    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.

  • LetrozoleDrug

    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.

  • TamoxifenDrug

    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.

Study groups in NCT03161353
Study groupRoleWhat they receive
Cohort AExperimentalCohorts 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".
Receives: Drug: Perjeta; Drug: Herceptin; Drug: Docetaxel; Drug: Carboplatin; Drug: Letrozole; Drug: Tamoxifen
Cohort BExperimentalCohorts 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".
Receives: Drug: Perjeta; Drug: Herceptin; Drug: Docetaxel; Drug: Carboplatin; Drug: Letrozole; Drug: Tamoxifen
Cohort CExperimentalcohorts 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.
Receives: Drug: Perjeta; Drug: Herceptin; Drug: Docetaxel; Drug: Carboplatin; Drug: Letrozole; Drug: Tamoxifen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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].

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  2. 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.

    Measured: After 3 years (36 months)

Secondary outcomes (18)

  1. pCR rates in the breast and axilla (ypTO/isN0)

    pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status).

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  2. pCR rates in the breast (ypT0/is)

    pCR rates in the breast (ypT0/is) (cohort A; cohort B; cohorts A/B by PET responder status).

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  3. RCB score (residual cancer burden)

    RCB score (cohort A; cohort B; cohorts A/B by PET responder status).

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  4. pCR rates in the breast and axilla

    pCR rates in the breast and axilla (ypT0/isN0) (cohort A; cohort B; cohorts A/B by PET responder status; HR status, HER2 status and tumor stage).

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  5. Rate of breast conserving surgery

    Rate of breast conserving surgery (cohort A; cohort B; cohorts A/B by PET responder status).

    Measured: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)

  6. 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).

    Measured: After cycle 2 (each cycle 21 days- After 42 days approximately)

  7. Optimal 18F-FDG PET/CT cut-off for pCR

    Optimal 18F-FDG PET/CT cut-off for pCR (cohort A; cohort B).

    Measured: After cycle 2 (each cycle 21 days-After 42 days approximately)

  8. 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.

    Measured: After cycle 2 (each cycle 21 days- After 42 days approximately)

  9. MRI response rate

    MRI response rate (according to the RECIST criteria version 1.1) (cohort A; cohort B; cohorts A/B by PET responder status).

    Measured: After two cycles of neoadjuvant therapy, and prior to surgery (each cycle 21 days)

  10. 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; cohorts A/B by PET responder status). 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.

    Measured: Baseline, cycle 3 (after 63 days approximately), before surgery and end of study through study completion (after cycle 18- after 12 months approximately)

  11. 3, 5, and 7-year iDFS

    3, 5, and 7-year iDFS (cohort A; cohort B [with the exception of 3-year iDFS]; cohorts A/B by PET responder status, HR status, and HER2 status).

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

  12. 3,5 and 7-year DDFS (DDFS:Distant disease-free survival)

    3, 5, and 7-year DDFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

  13. 3, 5 and 7-year DFS (DFS:Disease-free survival)

    3, 5, and 7-year DFS (cohort A; cohort B; cohorts A/B by PET responder status, HR status, and HER2 status).

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

  14. 3, 5 and 7-year (OS: overall survival)

    3, 5, and 7-year OS (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status)

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

  15. PFS (cohort C) (PFS: Progression-free survival)

    PFS (patients with subclinical M1 at baseline by 18F-FDG PET/CT - cohort C).

    Measured: Until progression or death, assessed up to approximately 84 months

  16. Adverse events

    Adverse events, grade 3-4 adverse events, related adverse events, serious adverse events, related serious adverse events, and adverse events leading to discontinuation (cohort A; cohort B; cohort C; cohorts A/B by PET responder status, HR status, and HER2 status).

    Measured: Until progression or death, assessed up to approximately 84 months

  17. 3, 5, and 7-year EFS

    3, 5, and 7-year EFS (cohort A; cohort B).

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

  18. To assess 3, 5, and 7-year adapted iDFS, DDFS, and DFS

    To assess 3, 5, and 7-year adapted iDFS, DDFS, and DFS on patients with subclinical M1 at baseline by 18F-FDG PET/CT - cohort C.

    Measured: After 3, 5 and 7 years (After 36, 60 and 80 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2017
  2. Study start26 Jun 2017
  3. Primary completion1 Nov 2023
  4. Study completion1 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Enrolment
377 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03161353
Sponsor's protocol ID
MedOPP096
Other IDs
2016-002676-27, 2016
Acronym
PHERGain
Status last verified
Apr 2025
First submitted
15 May 2017
Last updated
23 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Perez-Garcia JM, Cortes J, Ruiz-Borrego M, Stradella A, Bermejo B, Escriva-de-Romani S, Reboredo C, Albacar C, Martinez-Janez N, Iranzo V, Ribelles N, Dalenc F, Prat A, Schmid P, Gebhart G, Marme F, Di Cosimo S, Braga S, Colleoni M, Antonarelli G, Notini G, Gion M, Garcia-Mosquera JJ, Sanz L, Martinez-Garcia E, Meya A, Dustin D, Amaya-Garrido A, Guerrero-Martinez JA, Alcala-Lopez D, Rodriguez-Morato J, Mina L, Mancino M, Llombart-Cussac A. 5-year outcomes of chemotherapy de-escalation in HER2-positive early breast cancer and exploratory circulating tumor DNA analyses from the randomized phase 2 PHERGain trial. Nat Med. 2026 Oct 29. doi: 10.1038/s41591-026-04723-w. Online ahead of print.

    PubMed 42957778

  • Llombart-Cussac A, Prat A, Perez-Garcia JM, Mateos J, Pascual T, Escriva-de-Romani S, Stradella A, Ruiz-Borrego M, de Las Heras BB, Keyaerts M, Galvan P, Braso-Maristany F, Garcia-Mosquera JJ, Guiot T, Gion M, Sampayo-Cordero M, Di Cosimo S, Perez-Escuredo J, de Frutos MA, Cortes J, Gebhart G. Clinicopathological and molecular predictors of [18F]FDG-PET disease detection in HER2-positive early breast cancer: RESPONSE, a substudy of the randomized PHERGain trial. Eur J Nucl Med Mol Imaging. 2024 Jul;51(9):2733-2743. doi: 10.1007/s00259-024-06683-0. Epub 2024 Apr 8.

    PubMed 38587643

  • Perez-Garcia JM, Cortes J, Ruiz-Borrego M, Colleoni M, Stradella A, Bermejo B, Dalenc F, Escriva-de-Romani S, Calvo Martinez L, Ribelles N, Marme F, Cortes A, Albacar C, Gebhart G, Prat A, Kerrou K, Schmid P, Braga S, Di Cosimo S, Gion M, Antonarelli G, Popa C, Szostak E, Alcala-Lopez D, Gener P, Rodriguez-Morato J, Mina L, Sampayo-Cordero M, Llombart-Cussac A; PHERGain Trial Investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Lancet. 2024 Apr 27;403(10437):1649-1659. doi: 10.1016/S0140-6736(24)00054-0. Epub 2024 Apr 3.

    PubMed 38582092

  • Gebhart G, Keyaerts M, Guiot T, Flamen P, Ruiz-Borrego M, Stradella A, Bermejo B, Escriva-de-Romani S, Calvo Martinez L, Ribelles N, Fernandez-Abad M, Albacar C, Colleoni M, Garrigos L, Atienza de Frutos M, Dalenc F, Prat A, Marme F, Schmid P, Kerrou K, Braga S, Gener P, Sampayo-Cordero M, Cortes J, Perez-Garcia JM, Llombart-Cussac A. Optimal [18F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial. J Nucl Med. 2024 May 1;65(5):708-713. doi: 10.2967/jnumed.123.266384.

    PubMed 38575192

  • 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.

    PubMed 36300423

  • 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.

    PubMed 34019819

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Perjeta, Herceptin and Docetaxel in people with Breast Cancer, run by MedSIR at 56 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in Spain, France, Italy, Portugal, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the rate of pCR (time frame: After Cycle 6 or 8 (each cycle 21 days- After 4.2 or 5.6 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03161353, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.

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