Study of Palbociclib and Trastuzumab With Endocrine Therapy in HER2-positive Metastatic Breast Cancer

NCT02448420 | Completed Phase 2 DMC

• 2 other identifiers: SOLTI-13032014-005006-38
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 35

Brief Summary

PATRICIA is a phase II, open-label, multicentre, Simon's two-stage-design study of the combination of palbociclib plus trastuzumab, with or without letrozole, in post-menopausal patients with HER2-positive locally advanced or metastatic breast cancer (MBC) who have received chemotherapy and treatment with trastuzumab for their metastatic disease. Cohorts A, B1, and B2 based on their HR status and treatment allocation were planned. Cohort A included patients with hormone receptor-negative, HER2 positive breast cancer, who received trastuzumab + palbociclib. Cohort B1 included patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib. Cohort B2 included patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole. The aim of the PATRICIA study is to test the hypothesis that the addition of Palbociclib to standard therapy is well tolerated and can provide a benefit in progression-free survival. Based on interim results from this trial that support the benefit of CDK4 / 6 inhibition in luminal disease, two additional cohorts will be included.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival at 6 months

  For cohorts A,B1 and B2: This was defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria), 6 months after randomization.

  From randomization date to date of first documentation of progression or death , whichever came first, assessed up to 6 months.

• Progression-Free Survival (PFS)as Assessed by the Investigator [ Time Frame: From randomization date to date of first documentation of progression or death

  For cohorts C: This will be defined as the proportion of patients alive and without progression (according to RECIST v1.1 criteria)

  From randomization date to date of first documentation of progression or death , whichever came first, assessed up to 4 years

Secondary Outcomes (12)

• Rate of Disease control rate (DCR) in treatment arms (A and B)

  up to 5 years

• Rate of Overall tumour objective response rate (ORR) in treatment arms (A and B).

  up to 5 years

• Evaluation of time to progression (Cohorts A and B)

  up to 5 years

• Cardiac Safety profile in arms A and B: Percentage of Participants with cardiac adverse events

  up to 5 years

• Overall Survival in treatment arms (Cohorts A and B).

  up to 5 years

Study Arms (5)

Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed)

EXPERIMENTAL

Patients with hormone receptor-negative, HER2 positive breast cancer, who received trastuzumab + palbociclib. Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.

Drug: Palbociclib; Drug: Trastuzumab

Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed)

EXPERIMENTAL

Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib. Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.

Drug: Palbociclib; Drug: Trastuzumab

Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed)

EXPERIMENTAL

Patients with hormone receptor-positive, HER2 positive breast cancer, who received trastuzumab + palbociclib + letrozole Palbociclib: oral, 200 mg/day for 2 weeks, followed by 1 week off. Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks. Letrozole: daily oral dose of 2.5 mg.

Drug: Palbociclib; Drug: Trastuzumab; Drug: Endocrine therapy

Arm C1: Palbociclib, trastuzumab and endocrine therapy

EXPERIMENTAL

HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive trastuzumab + palbociclib + endocrine therapy Trastuzumab: intravenous trastuzumab loading dose of 8mg/kg followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks. Palbociclib: oral, 125 mg/d for 3 weeks, followed by one week off, in 4-week cycles. Endocrine therapy: either an Aromatase Inhibitor, Fulvestrant, or Tamoxifen.

Drug: Palbociclib; Drug: Trastuzumab; Drug: Endocrine therapy

Arm C2: Treatment based of physician's choice

ACTIVE COMPARATOR

HR-positive, HER2 positive, Luminal intrinsic subtype determined by PAM50 who will receive treatment based on physician's choice from the following options: TDM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin or a taxane) in combination with trastuzumab or endocrine therapy (Aromatase Inhibitor, Fulvestrant or Tamoxifen) in combination with trastuzumab.

Drug: Trastuzumab; Drug: Endocrine therapy; Drug: Chemotherapy; Drug: Antibody-Drug Conjugates

Interventions

Palbociclib DRUG

Cohort A, B1 y B2: Palbociclib oral dose of 200 mg/day for 2 weeks, followed by 1 week off. Cohort C1: Palbociclib oral dose 125 mg/d for 3 weeks, followed by one week off, in 4-week cycles.

Also known as: Ibrance

Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed); Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed); Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed); Arm C1: Palbociclib, trastuzumab and endocrine therapy

Trastuzumab DRUG

Loading dose of 8mg/kg intravenous (iv) followed by 6 mg/kg once every 3 weeks; or subcutaneous trastuzumab 600mg every 3 weeks.

Also known as: Herceptin

Arm A: HER2-positive/Hormone receptor-negative (Recruitment Closed); Arm B1: HER2+/Hormone receptor-positive (Recruitment Closed); Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed); Arm C1: Palbociclib, trastuzumab and endocrine therapy; Arm C2: Treatment based of physician's choice

Endocrine therapy DRUG

Non-steroidal AIs (anastrozole, letrozole); steroidal AI (exemestane); Fulvestrant or Tamoxifen

Also known as: ET

Arm B2:HER+/HR+: trastuzumab + palbociclib +letrozole (Recruitment Closed); Arm C1: Palbociclib, trastuzumab and endocrine therapy; Arm C2: Treatment based of physician's choice

Chemotherapy DRUG

Gemcitabine, vinorelbine, capecitabine, eribulin or a taxane

Also known as: CT

Arm C2: Treatment based of physician's choice

Antibody-Drug Conjugates DRUG

3.6 mg/kg iv every 3 weeks

Also known as: Trastuzumab emtansine (TDM-1)

Arm C2: Treatment based of physician's choice

Eligibility Criteria

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

You may qualify if:

• For Cohorts A and B (Recruitment Closed)
• Written signed Informed Consent for all study procedures in accordance with the local administrative requirements prior to starting the protocol-specific procedures.
• Female patients
• Age 18 years or older
• ECOG performance status 0 or 1.
• Invasive HER2 positive breast cancer, according to the local laboratory, defined according to ASCO/CAP criteria as:
• + overexpression on immunohistochemistry (\>10% of invasive tumor cells with intensive, circumferential membrane staining)
• Positive in situ hybridization (FISH/CISH/SISH) in \>10% of invasive tumor cells, having counted at least 20 cells in the area and based on:
• i. Single-probe HER2 gene copy number ≥ 6 signals/cell. ii. Dual-probe HER2/CEP17 ratio ≥ 2.0 with a mean HER2 gene copy number ≥ 4.0 signals/cell; HER2/CEP17 ratio ≥ 2.0 and \< 4.0 signals/cell; and HER2/CEP17 ratio \< 2.0 and ≥ 6.0 signals/cell.
• Known hormone receptor, determined locally according to ASCO/CAP guidelines; OR or PgR considered positive in case of ≥1% of cell nuclei positive.
• Histologically-confirmed adenocarcinoma of the breast, metastatic or locally advanced.
• Patients with locally advanced disease must have recurrent or progressive disease unsuitable for resection with curative intent. Patients with standard curative options available will not be eligible.
• In patients with bilateral breast cancer, HER2+ positivity must be demonstrated in both sites or in a metastatic biopsy.
• All patients must have received at least 2 (maximum 4) previous lines of systemic treatment for metastatic or locally advanced disease, at least one of which must have included trastuzumab. Previous use of other anti-HER2 treatment, alone or in combination with chemotherapy, is permitted, including lapatinib, neratinib, pertuzumab or T-DM1. Previous use of any chemotherapy or hormone agent is permitted.
• Tumour tissue available for biomarker analysis, obtained from metastatic lesions (preferably) or from the primary tumor.

You may not qualify if:

• For cohorts A, B (Recruitment Closed)
• Treatment with any investigational anticancer drug within 14 days of the start of study treatment.
• Patient has received more than 4 previous lines of treatment (anti-HER2 drug +/- chemotherapy) for metastatic breast cancer or locally advanced disease. Exclusively hormonal treatments will not be taken into account.
• Previous treatment with a cyclin-dependent kinase inhibitor.
• History of other malignant tumours in the past 5 years, with the exception of adequately treated in situ carcinoma of the cervix, non-melanoma carcinoma of the skin, uterine cancer in stage I or other malignant tumours with an expected curative outcome.
• History of exposure to cumulative anthracycline doses greater than follows:
• Adriamycin \> 400 mg/m2
• Epirubicin \> 720 mg/m2
• Mitoxantrone \> 120 mg/m2
• Idarubicin \> 90 mg/m2
• If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 400 mg/m2 of adriamycin.
• Cardiopulmonary dysfunction, defined as:
• Uncontrolled hypertension (systolic \> 150 mmHg and/or diastolic \> 100 mmHg) despite optimum medical treatment.
• Angina pectoris or arrhythmia poorly controlled with optimum medical treatment.
• History of congestive heart failure NCI CTCAE version 4.0 grade ≥ 3 NYHA class ≥ 2.

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead

Study Sites (35)

ICO-Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital General De Catalunya

Sant Cugat del Vallès, Barcelona, 08195, Spain

Location

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, 28933, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06080, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario del Vall d' Hebron

Barcelona, Spain

Location

ICO Hospitalet

Barcelona, Spain

Location

Hospital de Basurto

Bilbao, Spain

Location

Consorcio Hospitalario Provincial de Castellón

Castellon, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital Reina Sofía de Córdoba

Córdoba, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

HU Clínico San Cecilio

Granada, 18016, Spain

Location

Complejo Asistencial Universitario de León

León, 24071, Spain

Location

HU Arnau de Vilanova Lleida

Lleida, 25198, Spain

Location

Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, Spain

Location

H. Severo Ochoa

Madrid, Spain

Location

H. U Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario Doce de Octubre

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Virgen Universitario Virgen de Macarena

Seville, 41009, Spain

Location

Hospital Quirón Salud Sagrado Corazón

Seville, 41013, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario Sant Joan de Reus

Tarragona, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Hospital Álvaro Cunqueiro

Vigo, Spain

Location

Related Publications (2)

• Ciruelos E, Villagrasa P, Pascual T, Oliveira M, Pernas S, Pare L, Escriva-de-Romani S, Manso L, Adamo B, Martinez E, Cortes J, Vazquez S, Perello A, Garau I, Mele M, Martinez N, Montano A, Bermejo B, Morales S, Echarri MJ, Vega E, Gonzalez-Farre B, Martinez D, Galvan P, Canes J, Nuciforo P, Gonzalez X, Prat A. Palbociclib and Trastuzumab in HER2-Positive Advanced Breast Cancer: Results from the Phase II SOLTI-1303 PATRICIA Trial. Clin Cancer Res. 2020 Nov 15;26(22):5820-5829. doi: 10.1158/1078-0432.CCR-20-0844. Epub 2020 Sep 16.

  PMID: 32938620 BACKGROUND

• Peddi PF, Slamon DJ. Frontiers in HER2-positive breast cancer in 2020. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):48-52. doi: 10.1097/GCO.0000000000000677.

  PMID: 33369581 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Trastuzumab; Drug Therapy; Immunoconjugates; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Eva Ciruelos, MD

  SOLTI Breast Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: When the recruitment cohorts C begins, the recruitment in cohorts A and B will be closed.

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 19, 2015
• Study Start: July 1, 2015
• Primary Completion: September 29, 2023
• Study Completion: November 30, 2023
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

ES (35)