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

NCT ID: NCT03272477

Last Updated: 2024-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

257 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-05

Study Completion Date

2024-03-04

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Paclitaxel+Trastuzumab+Pertuzumab

Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.

Adjuvant Therapy: Standard of care

Group Type ACTIVE_COMPARATOR

Perjeta Injectable Product

Intervention Type 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.)

Herceptin

Intervention Type 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.)

Tamoxifen

Intervention Type DRUG

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

Paclitaxel

Intervention Type 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.

Epirubicin

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type 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

Anastrozole

Intervention Type DRUG

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

Letrozole

Intervention Type DRUG

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

Exemestane

Intervention Type DRUG

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

Leuprorelin acetate

Intervention Type 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.

Goserelin

Intervention Type 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.

Biopsy

Intervention Type DIAGNOSTIC_TEST

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

Surgery

Intervention Type PROCEDURE

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

Endocrine+Trastuzumab+Pertuzumab

Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.

Adjuvant Therapy: Standard of care

Group Type EXPERIMENTAL

Perjeta Injectable Product

Intervention Type 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.)

Herceptin

Intervention Type 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.)

Epirubicin

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type 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

Anastrozole

Intervention Type DRUG

1mg per day for 12 weeks in neoadjuvant therapy phase; 1mg per day for a total of 40 weeks max. in adjuvant therapy phase

Letrozole

Intervention Type DRUG

2,5 mg per day for 12 weeks in neoadjuvant therapy phase; 2,5 mg perday for a total of 40 weeks max. in adjuvant therapy phase

Exemestane

Intervention Type DRUG

25mg/day for 12 weeks in neoadjuvant therapy phase; 25mg/day for a total of 40 weeks max. in adjuvant therapy phase

Paclitaxel

Intervention Type DRUG

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

Tamoxifen

Intervention Type DRUG

20mg per day (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase.

Leuporelin acetate

Intervention Type 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).

Goserelin

Intervention Type DRUG

3,5mg every 28 days 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).

Biopsy

Intervention Type DIAGNOSTIC_TEST

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

Surgery

Intervention Type PROCEDURE

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

Interventions

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Perjeta Injectable Product

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.)

Intervention Type DRUG

Herceptin

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.)

Intervention Type DRUG

Tamoxifen

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

Intervention Type DRUG

Paclitaxel

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.

Intervention Type DRUG

Epirubicin

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Anastrozole

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

Intervention Type DRUG

Letrozole

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

Intervention Type DRUG

Exemestane

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

Intervention Type DRUG

Leuprorelin acetate

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.

Intervention Type DRUG

Goserelin

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.

Intervention Type DRUG

Anastrozole

1mg per day for 12 weeks in neoadjuvant therapy phase; 1mg per day for a total of 40 weeks max. in adjuvant therapy phase

Intervention Type DRUG

Letrozole

2,5 mg per day for 12 weeks in neoadjuvant therapy phase; 2,5 mg perday for a total of 40 weeks max. in adjuvant therapy phase

Intervention Type DRUG

Exemestane

25mg/day for 12 weeks in neoadjuvant therapy phase; 25mg/day for a total of 40 weeks max. in adjuvant therapy phase

Intervention Type DRUG

Paclitaxel

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

Intervention Type DRUG

Tamoxifen

20mg per day (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase.

Intervention Type DRUG

Leuporelin acetate

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).

Intervention Type DRUG

Goserelin

3,5mg every 28 days 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).

Intervention Type DRUG

Biopsy

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

Intervention Type DIAGNOSTIC_TEST

Surgery

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

Intervention Type PROCEDURE

Other Intervention Names

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Pertuzumab Trastuzumab

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Previous or concurrent treatment with cytotoxic agents for any reason
* Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project within 30 days prior to study entry is excluded
* Male breast cancer
* Concurrent pregnancy
* Breastfeeding
* Sequential breast cancer
* Reasons indicating risk of poor compliance
* Known polyneuropathy ≥ grade 2
* Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to:

* Uncompensated chronic heart failure or systolic dysfunction (LVEF \< 55%, CHF NYHA classes II-IV),
* unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block,
* Angina pectoris within the last 6 months requiring anti-anginal medication,
* Clinically significant valvular heart disease,
* Evidence of myocardial infarction on electrocardiogram (ECG),
* Poorly controlled hypertension (e.g., systolic \> 180 mm Hg or diastolic \> 100 mm Hg).
* Inadequate organ function including but not confined to:

* hepatic impairment (Child Pugh Class C)
* pulmonary disease (severe dyspnea at rest requiring oxygen therapy)
* Abnormal blood values:

* Thrombocytopenia \> CTCAE grade 1
* Increases in ALT/AST \> CTCAE grade 1
* Hypokalaemia \> CTCAE grade 1
* Neutropenia \> CTCAE grade 1
* Anaemia \> CTCAE grade 1
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

WSG WOMEN´S HEALTHCARE STUDY GROUP

UNKNOWN

Sponsor Role collaborator

Cankado GmbH

INDUSTRY

Sponsor Role collaborator

Palleos Healthcare GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Iris Reiser, PhD

Role: STUDY_DIRECTOR

Palleos Healthcare GmbH

Locations

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Evangelisches Krankenhaus Bethesda Mönchengladbach

Mönchengladbach, , Germany

Site Status

Countries

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Germany

References

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Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PH002-TP-II

Identifier Type: -

Identifier Source: org_study_id

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