To Reduce the Use of Chemotherapy in Postmenopausal Patients With ER-positive and HER2-positive Breast Cancer (TOUCH)

NCT03644186 | Completed Phase 2 Results DMC

• 2 other identifiers: IBCSG 55-172017-005067-40
• Study Type: interventional
• Target: 147
• Locations: 4 countries
• Sites: 54

Brief Summary

This is a phase II open-label, multicentre, randomized trial. The study assesses the treatment of postmenopausal patients with hormone receptor positive/HER2 positive early breast cancer with neoadjuvant palbociclib in combination with hormonal therapy and HER2 blockade, versus the treatment with paclitaxel in combination with HER2 blockade.

Conditions

Breast Cancer; Estrogen Receptor Positive Tumor; HER2-positive Breast Cancer

Keywords

hormone receptor positive early breast cancer; HER2 receptor positive early breast cancer

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  Pathological complete response (pCR) is defined as absence of invasive tumour cells in the breast and in the axillary lymph nodes at the time of surgery (ypT0/ypTis ypN0) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual. The presence of in situ cancer after trial treatment in the absence of residual invasive disease constitutes a pCR.

  Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks; up to 21 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped; up to 30 weeks.

Secondary Outcomes (3)

• Pathological Complete Response (pCR) in the Breast

  Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks; up to 21 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped; up to 30 weeks.

• Objective Response

  Tumor assessments were performed by ultrasound and mammography at screening (prior to treatment start), and before surgery; measurements by caliper were assessed at the same time points and at the end of cycle 2 (28 days/cycle), approximately 56 days.

• Rate of Breast Conserving Surgery (BCS)

  From randomization until completion of study, up to 20 months

Study Arms (2)

Paclitaxel plus trastuzumab and pertuzumab

ACTIVE COMPARATOR

Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses.

Drug: Paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab

Palbociclib plus letrozole plus trastuzumab and pertuzumab

EXPERIMENTAL

Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses.

Drug: Palbociclib; Drug: Letrozole; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Paclitaxel DRUG

Chemotherapy plus HER2 Blockade

Also known as: Paclitaxel Sandoz

Paclitaxel plus trastuzumab and pertuzumab

Trastuzumab DRUG

Chemotherapy plus HER2 Blockade

Also known as: Herceptin

Paclitaxel plus trastuzumab and pertuzumab

Pertuzumab DRUG

Chemotherapy plus HER2 Blockade

Also known as: Perjeta

Paclitaxel plus trastuzumab and pertuzumab

Palbociclib DRUG

CDK Inhibition plus Hormonal Therapy plus HER2 Blockade

Also known as: Ibrance

Palbociclib plus letrozole plus trastuzumab and pertuzumab

Letrozole DRUG

CDK Inhibition plus Hormonal Therapy plus HER2 Blockade

Also known as: Femara

Palbociclib plus letrozole plus trastuzumab and pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive breast cancer, with the following characteristics:
• Early breast cancer with tumor size \>1 cm (as measured by at least one of the required examination methods of clinical examination, mammography and ultrasonography);
• No clinical evidence of regional lymph node metastasis (via physical and/or radiological exam) (cN0) OR
• Clinical evidence of cN1 status, defined by nodal involvement limited to clinically or radiologically detectable metastasis to movable ipsilateral level I, II axillary lymph node(s)
• No evidence of metastasis (M0).
• Postmenopausal, defined by women with:
• Prior bilateral surgical oophorectomy; OR
• Amenorrhea and age ≥60 years; OR
• Age \<60 years and amenorrhea for 12 or more consecutive months in the absence of alternative pathological or physiological cause (including chemotherapy, tamoxifen, toremifene, ovarian suppression, or hormonally-based contraception) plus FSH and serum estradiol levels within the laboratory's reference ranges for postmenopausal women
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Primary tumor must have positive estrogen receptor (ER) ≥10%
• Primary tumor must be HER2-positive (by IHC and/or ISH)
• Baseline LVEF ≥55% measured by Echocardiography (preferred) or MUGA scan
• Normal hematologic status:
• Absolute neutrophil count ≥1500/mm3 (1.5 × 109/L);

You may not qualify if:

• Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) (T4 according to AJCC 8th edition cancer staging TNM)
• Inflammatory breast cancer
• Bilateral invasive breast cancer
• Received any prior treatment for primary invasive breast cancer
• Any active tumor of non-breast-cancer histology
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification ≥II), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
• Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
• Contraindications or known hypersensitivity to any of the trial medications or excipients
• Treatment with any investigational agents within 30 days prior to expected start of trial treatment
• Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post major bowel resection
• Evidence via physical and/or radiological exam of cN2 or cN3 nodal involvement defined by: metastasis to ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted, OR involvement of ipsilateral infraclavicular, internal mammary and/or supraclavicular lymph node(s)

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Pfizer: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (54)

AZ Klina, Augustijinslei 100

Brasschaat, 2930, Belgium

Location

Jules Bordet Institute

Brussels, 1000, Belgium

Location

CHR de la Citadelle, Boulevard du XIIe de Ligne, 1

Liège, 4000, Belgium

Location

Clinique Saint- Joseph, Rue de Hesbaye 75

Liège, 4000, Belgium

Location

Clinique Saint Elizabeth, Place Louise Godin 15

Namur, 5000, Belgium

Location

AZ Nikolaas, Moerlandstrat 1

Sint-Niklaas, 9100, Belgium

Location

Institut Sainte Catherine

Avignon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre Hospitalier Le Mans

Le Mans, France

Location

Centre Léon Berard

Lyon, France

Location

ICM Val d'Aurelle

Montpellier, France

Location

Institut de Cancérologie de l'Ouest (ICO)

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, France

Location

Institut Curie - Site de Paris

Paris, France

Location

Centre Hospitalier Annecy Genevois

Pringy, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie - Site Saint Cloud

Saint-Cloud, 92210, France

Location

Clinique Pasteur

Toulouse, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Clinica Oncologica-Ospedali Riuniti Ancona, Via Conca n.71,

Torrette, Ancona, 60020, Italy

Location

Istituto scientifico Romagnolo per lo studio e la cura,Via Piero Maroncelli 40

Meldola, Forli, 47014, Italy

Location

U.O Medicina Oncologica Ospedale di Carpi, Via G. Molinari, 2

Carpi, Modena, 41012, Italy

Location

Centro di Riferimento Oncologico (CRO), Via Franco Gallini 2

Aviano, Pordenone, 33081, Italy

Location

ASO "SS Antonio e Biagio Cesare Arrigo, Via Venezia 16

Alessandria, 15121, Italy

Location

Ospedali Riuniti di Bergamo, A.O.Papa Giovanni XXIII, Piazza OMS1

Bergamo, 24127, Italy

Location

Ospedale S. Orsola-Malpighi, Viale Ercolani 4/2

Bologna, 40138, Italy

Location

Comprensorio Sanitario Bolzano, Via Lorenz Bohler, 5

Bolzano, 39100, Italy

Location

ASST Spedali Civili Brescia, Piazzale Spedali Civili n.1

Brescia, 25123, Italy

Location

E.O. Ospedali Galliera, Mura delle Cappuccine, 14

Genova, 16128, Italy

Location

Ospedale Policlinico San Martino,Largo Rosanna Benzi,10

Genova, 16132, Italy

Location

Ospedale Civile di Lecco,Via della Filanda 14

Lecco, 23900, Italy

Location

Milano, IEO, Via Ripamonti 435

Milan, 20141, Italy

Location

Università del Piemonte Orientale - SCDU Oncologia, Corso Mazzini 18

Novara, 28100, Italy

Location

Azienda Ospedaliero-Universitaria di Parma, via Gramsci 14

Parma, 43126, Italy

Location

Istituti Clinici Scientifici Maugeri SpA-SB,Via Salvatore Maugeri N° 10

Pavia, 27100, Italy

Location

A.O. Universitaria Pisana Ospedale Santa Chiara Pisa, Via Roma 67

Pisa, 56125, Italy

Location

Hospital of Prato, Via Dolce dei Mazzamuti, 7

Prato, 59100, Italy

Location

Santa Maria delle Croci Hospital, Viale Randi 5

Ravenna, 48121, Italy

Location

UO Oncologia, Rimini Hospital, Via Settembrini 2

Rimini, 47037, Italy

Location

Azienda Ospedaliero-Universitaria di Udine, Piazzale S.M. Misericordia 15

Udine, 33100, Italy

Location

AO Universitaria Ospedale Di Circolo e Fondazione,v.le L. Borri, 57

Varese, 21100, Italy

Location

Kantonsspital Baden AG

Baden, Aarau, 5400, Switzerland

Location

Universitatsspital Basel, Petersgraben 4

Basel, Canton of Basel-City, 4031, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Canton of Zurich, 8401, Switzerland

Location

University Hospital Zurich, Frauenklinikstrasse 10

Zurich, Canton of Zurich, 8091, Switzerland

Location

Oncology Institute of Southern Switzerland (IOSI), Ospedale San Giovanni, IOSI

Bellinzona, Canton Ticino, 6500, Switzerland

Location

Brustzentrum Thurgau / Kantonsspital Frauenfeld, Pfaffenholzstrasse 4

Frauenfeld, Thurgau, 8501, Switzerland

Location

Inselspital Bern

Bern, Switzerland

Location

HFR Freiburg - Kantonsspital

Fribourg, 1708, Switzerland

Location

University Hospital Geneva

Geneva, Switzerland

Location

Kantonsspital St. Gallen, Rorschacher Strasse 95

Sankt Gallen, 9007, Switzerland

Location

Brust-Zentrum AG, Seefeldstrasse 214

Zurich, 8008, Switzerland

Location

Related Publications (14)

• Biganzoli L, Wildiers H, Oakman C, Marotti L, Loibl S, Kunkler I, Reed M, Ciatto S, Voogd AC, Brain E, Cutuli B, Terret C, Gosney M, Aapro M, Audisio R. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol. 2012 Apr;13(4):e148-60. doi: 10.1016/S1470-2045(11)70383-7. Epub 2012 Mar 30.

  PMID: 22469125 BACKGROUND

• Biganzoli L, Aapro M, Loibl S, Wildiers H, Brain E. Taxanes in the treatment of breast cancer: Have we better defined their role in older patients? A position paper from a SIOG Task Force. Cancer Treat Rev. 2016 Feb;43:19-26. doi: 10.1016/j.ctrv.2015.11.009. Epub 2015 Dec 15.

  PMID: 26827689 BACKGROUND

• Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012 Oct 4;490(7418):61-70. doi: 10.1038/nature11412. Epub 2012 Sep 23.

  PMID: 23000897 BACKGROUND

• Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-439. doi: 10.1016/S1470-2045(15)00613-0. Epub 2016 Mar 3.

  PMID: 26947331 BACKGROUND

• Demidenko E. Sample size and optimal design for logistic regression with binary interaction. Stat Med. 2008 Jan 15;27(1):36-46. doi: 10.1002/sim.2980.

  PMID: 17634969 BACKGROUND

• Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77. doi: 10.1186/bcr2419.

  PMID: 19874578 BACKGROUND

• Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Dieras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303.

  PMID: 27959613 BACKGROUND

• Herschkowitz JI, He X, Fan C, Perou CM. The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas. Breast Cancer Res. 2008;10(5):R75. doi: 10.1186/bcr2142. Epub 2008 Sep 9.

  PMID: 18782450 BACKGROUND

• Jenkins EO, Deal AM, Anders CK, Prat A, Perou CM, Carey LA, Muss HB. Age-specific changes in intrinsic breast cancer subtypes: a focus on older women. Oncologist. 2014 Oct;19(10):1076-83. doi: 10.1634/theoncologist.2014-0184. Epub 2014 Aug 20.

  PMID: 25142841 BACKGROUND

• Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. doi: 10.1200/JCO.2009.23.3734. Epub 2009 Sep 28.

  PMID: 19786658 BACKGROUND

• Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. doi: 10.1200/JCO.2008.20.6847. Epub 2009 Sep 28.

  PMID: 19786670 BACKGROUND

• Malorni L, Piazza S, Ciani Y, Guarducci C, Bonechi M, Biagioni C, Hart CD, Verardo R, Di Leo A, Migliaccio I. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer. Oncotarget. 2016 Sep 13;7(42):68012-68022. doi: 10.18632/oncotarget.12010.

  PMID: 27634906 BACKGROUND

• Miles D, Baselga J, Amadori D, Sunpaweravong P, Semiglazov V, Knott A, Clark E, Ross G, Swain SM. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast Cancer Res Treat. 2013 Nov;142(1):89-99. doi: 10.1007/s10549-013-2710-z. Epub 2013 Oct 16.

  PMID: 24129974 BACKGROUND

• Witkiewicz AK, Ertel A, McFalls J, Valsecchi ME, Schwartz G, Knudsen ES. RB-pathway disruption is associated with improved response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2012 Sep 15;18(18):5110-22. doi: 10.1158/1078-0432.CCR-12-0903. Epub 2012 Jul 18.

  PMID: 22811582 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; pertuzumab; palbociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Heidi Roschitzki
• Organization: ETOP IBCSG Partners Foundation

TOUCH-monitoring@etop.ibcsg.org

+41 31 511 94 00

Study Officials

• Laura Biganzoli, MD

  USL4 Hospital of Prato, Italy

  STUDY CHAIR

• Etienne Brain, MD

  Institut Curie, Paris, France

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2018
• First Posted: August 23, 2018
• Study Start: April 16, 2019
• Primary Completion: January 3, 2023
• Study Completion: April 14, 2023
• Last Updated: December 13, 2024
• Results First Posted: December 13, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (22); CH (11); BE (6); FR (15)