Clinical trial NCT03272477: 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
Official title: A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard (Neo)Adjuvant Treatment in Patients With Operable HER2+/HR+ Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: hormone receptor positive
human epidermal growth factor receptor 2 positive
Early breast cancer
HR+/HER2+
Lead sponsor: Palleos Healthcare GmbH
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
name: WSG WOMEN´S HEALTHCARE STUDY GROUP
name: Cankado GmbH
First posted: 2017-09-05
Enrollment: 257
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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
  * Patients need to fulfill adequate blood count and organ function to receive chemotherapy (see 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Pathological complete response (pCR)
timeFrame: 14 weeks after start of therapy treatment
Secondary outcomes:
measure: Health-related quality of life using EORTC QBL-BR-23 scale
timeFrame: 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
measure: Health-related quality of life using EQ5D-5L scale
timeFrame: 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
measure: Health-related quality of life using EORTC QLQ-C30 scale
timeFrame: 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
measure: Tumor size reduction by mammography
timeFrame: at screening visit and 12 weeks after start of therapy treatment
measure: Tumor size reduction by palpation and ultrasound
timeFrame: at screening visit and 4, 7 and 13 weeks after start of therapy treatment
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 60 months
measure: Duration of invasive disease-free survival
timeFrame: From date of treatment allocation until the date of first documented progression or secondary tumor or date of death from any cause, whichever came first, assessed up to 60 months (study duration including follow up)
measure: Number of mastectomies
timeFrame: 14 weeks after start of therapy treatment
measure: Ki67 level
timeFrame: 4 weeks after start of therapy treatment
measure: cDNA composition
timeFrame: at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment
Other outcomes:
Locations:
city: Mönchengladbach
country: Germany
facility: Evangelisches Krankenhaus Bethesda Mönchengladbach
Study officials:
affiliation: Palleos Healthcare GmbH
name: Iris Reiser, PhD
role: STUDY_DIRECTOR
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