Study to Compare Neoadjuvant Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy and Quality of Life Assessment Under Adjuvant Therapy in Operable HER2+/HR+ Breast Cancer Patients

NCT03272477 | Completed Phase 2 DMC

• 1 other identifier: PH002-TP-II
• Study Type: interventional
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, phase IIa, multicenter, randomized, open-label study comparing a pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40 additional weeks in patients with operable HER2+/HR+ breast cancer.

Conditions

Breast Neoplasms

Keywords

hormone receptor positive; human epidermal growth factor receptor 2 positive; Early breast cancer; HR+/HER2+

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  14 weeks after start of therapy treatment, tumor and lymph node biopsy is performed to reach the primary endpoint of pathological complete response (pCR) which is defined as the absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/is ypN0 in the current AJCC staging system). As secondary endpoint, also other response states will be taken into account: no invasive tumor in the complete resected breast specimen irrespective of the lymph node state following completion of neoadjuvant systemic therapy (ypT0/is, any ypN).

  14 weeks after start of therapy treatment

Secondary Outcomes (10)

• Health-related quality of life using EORTC QBL-BR-23 scale

  During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first

• Health-related quality of life using EQ5D-5L scale

  During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first

• Health-related quality of life using EORTC QLQ-C30 scale

  During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first

• Tumor size reduction by mammography

  at screening visit and 12 weeks after start of therapy treatment

• Tumor size reduction by palpation and ultrasound

  at screening visit and 4, 7 and 13 weeks after start of therapy treatment

Study Arms (2)

Paclitaxel+Trastuzumab+Pertuzumab

ACTIVE COMPARATOR

Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy. Adjuvant Therapy: Standard of care

Drug: Perjeta Injectable Product; Drug: Herceptin; Drug: Tamoxifen; Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Leuprorelin acetate; Drug: Goserelin; Diagnostic Test: Biopsy; Procedure: Surgery

Endocrine+Trastuzumab+Pertuzumab

EXPERIMENTAL

Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy. Adjuvant Therapy: Standard of care

Drug: Perjeta Injectable Product; Drug: Herceptin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Paclitaxel; Drug: Tamoxifen; Drug: Leuporelin acetate; Drug: Goserelin; Diagnostic Test: Biopsy; Procedure: Surgery

Interventions

Perjeta Injectable Product DRUG

Single dose of 840mg (loading dose) day1 cycle 1, 420mg at day1 of each subsequent cycle, every 3 weeks. (The latter cycle is called cycle of treatment and is to be given 4 times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)

Also known as: Pertuzumab

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Herceptin DRUG

Single dose of 8mg/kg (loading dose) day1 cycle 1; 6mg/kg at day1 of each subsequent cycle body weight every 3 weeks. (This is called cycle of treatment and is to be given four times in the neoadjuvant phase and 14 times in the adjuvant therapy phase.)

Also known as: Trastuzumab

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Tamoxifen DRUG

20 mg per day for a total of 40 weeks in the adjuvant therapy phase.

Paclitaxel+Trastuzumab+Pertuzumab

Paclitaxel DRUG

80mg/sqm, day one of each cycle, every week. This is called a cycle of treatment and is to be given for 12 weeks in neoadjuvant therapy phase.

Paclitaxel+Trastuzumab+Pertuzumab

Epirubicin DRUG

12 weeks (4cycles) of max. 90mg/sqm in adjuvant therapy phase

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Cyclophosphamide DRUG

12 weeks (4cycles) of 600 mg/sqm i.v. on day 1+8 or 12 weeks (4cycles) of 500 mg/sqm i.v. on day 1 in adjuvant therapy phase

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Anastrozole DRUG

1mg per day for a total of 40 weeks in adjuvant therapy phase

Paclitaxel+Trastuzumab+Pertuzumab

Letrozole DRUG

2,5 mg/day for a total of 40 weeks in adjuvant therapy phase

Paclitaxel+Trastuzumab+Pertuzumab

Exemestane DRUG

25mg/day for a total of 40 weeks in adjuvant therapy phase

Paclitaxel+Trastuzumab+Pertuzumab

Leuprorelin acetate DRUG

One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.

Paclitaxel+Trastuzumab+Pertuzumab

Goserelin DRUG

3,6mg every 28 days or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane, for a total of 40 weeks in the adjuvant therapy phase.

Paclitaxel+Trastuzumab+Pertuzumab

Leuporelin acetate DRUG

One injection of 3,75mg every month or 4 weeks in pre-menopausal women treated with aromatase inhibitors Anastrozole or Letrozole or Exemestane (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase).

Endocrine+Trastuzumab+Pertuzumab

Biopsy DIAGNOSTIC_TEST

Core biopsy at screening (outside of protocol), at week 4 after randomization, (at week 14 in addition if neoadjuvant phase is prolonged)

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Surgery PROCEDURE

Surgery at week 14 after randomization (or later, if neoadjuvant phase is prolonged)

Endocrine+Trastuzumab+Pertuzumab; Paclitaxel+Trastuzumab+Pertuzumab

Eligibility Criteria

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

You may qualify if:

• Female patients, age at diagnosis 18 years and older
• Histologically confirmed unilateral primary invasive carcinoma of the breast
• Patients must qualify for neoadjuvant treatment as follows:
• No clinical evidence for distant metastasis (M0)
• Clinical cT1c-T4a-c (participation of patients with tumors \> cT2 is strongly recommended) and no evidence for distant metastases (M0)
• All clinical N (participation of patients with cN+, also in case of cT1c, is strongly recommended)
• Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH

You may not qualify if:

• Tumor block available for central pathology review
• Performance Status ECOG ≤ 1 or KI ≥ 80%
• Negative pregnancy test (urine or serum) within 7 days prior to registration in premenopausal patients
• Patients of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) non-hormonal contraceptive measures during the study treatment and for 6 months following the last dose of study treatment (trastuzumab and pertuzumab) such as:
• Intrauterine device (IUD)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence
• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
• The patient must be accessible for treatment and follow-up
• LVEF \> 55%; LVEF within normal limits of each institution measured by echocardiography (within 42 days prior to randomization)
• Normal ECG (within 42 days prior to randomization)
• Known hypersensitivity reaction to the compounds or incorporated substances
• Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
• Non-operable breast cancer including inflammatory breast cancer

Sponsors & Collaborators

• Palleos Healthcare GmbH: lead
• Roche Pharma AG: collaborator
• WSG WOMEN´S HEALTHCARE STUDY GROUP: collaborator
• Cankado GmbH: collaborator

Study Sites (1)

Evangelisches Krankenhaus Bethesda Mönchengladbach

Mönchengladbach, 41061, Germany

Location

Related Publications (54)

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Tamoxifen; Paclitaxel; Epirubicin; Cyclophosphamide; Anastrozole; Letrozole; exemestane; Leuprolide; Goserelin; Biopsy; Surgical Procedures, Operative

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; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Investigative Techniques

Study Officials

• Iris Reiser, PhD

  Palleos Healthcare GmbH

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: September 5, 2017
• Study Start: October 5, 2017
• Primary Completion: July 14, 2020
• Study Completion: March 4, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)