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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 (TP-II)

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ClinicalTrials.gov Identifier: NCT03272477
Recruitment Status : Completed
First Posted : September 5, 2017
Last Update Posted : April 17, 2024
Sponsor:
Collaborators:
Roche Pharma AG
WSG WOMEN´S HEALTHCARE STUDY GROUP
Cankado GmbH
Information provided by (Responsible Party):
Palleos Healthcare GmbH

Tracking Information
First Submitted Date  ICMJE August 10, 2017
First Posted Date  ICMJE September 5, 2017
Last Update Posted Date April 17, 2024
Actual Study Start Date  ICMJE October 5, 2017
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2017)		 Pathological complete response (pCR) [ Time Frame: 14 weeks after start of therapy treatment ]
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
  • Health-related quality of life using EORTC QBL-BR-23 scale [ Time Frame: 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 ]
    Assessment of quality of life questions during the past week or during the past 4 weeks (depending on the questions) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
  • Health-related quality of life using EQ5D-5L scale [ Time Frame: 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 ]
    • questions about "self care", "usual activities", "pain /discomfort", anxiety/depression" are assessed on a 5 level-scale using tick boxes : "I have no problem"; "I have slight problems"; "I have moderate problems"; "I have severe problems" "I am unable"
    • assessment of the patient health (good or bad) is measured on a scale numbered from 0 to 100 (100 means the best heath and 0 means the worst)
  • Health-related quality of life using EORTC QLQ-C30 scale [ Time Frame: 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 ]
    • Assessment of quality of life questions (activities, breath, pain, sleep, appetite, vomiting, constipation, others..) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
    • Assessment of Overall health and overall quality of life during the past week is measured on a 7 level-scale going from 1 (very poor) to 7 (excellent)
  • Tumor size reduction by mammography [ Time Frame: at screening visit and 12 weeks after start of therapy treatment ]
    The diameters of the tumors in the breast will be measured in millimeter by mammography as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
  • Tumor size reduction by palpation and ultrasound [ Time Frame: at screening visit and 4, 7 and 13 weeks after start of therapy treatment ]
    The diameters of the tumors in the breast will be measured in millimeter by palpation and ultrasound as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
  • Overall survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months ]
    The overall survival is defined as time (days) between study treatment allocation and death of patient due to any cause.
  • Duration of invasive disease-free survival [ Time Frame: 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) ]
    Duration of invasive disease-free survival is defined as time (days) between study treatment allocation and relapse, secondary tumor event or death.
  • Number of mastectomies [ Time Frame: 14 weeks after start of therapy treatment ]
    The number of mastectomies will be determined at time of surgery (week 14 and week 18)
  • Ki67 level [ Time Frame: 4 weeks after start of therapy treatment ]
    The level of Ki67 in biopsie material will be measured at week 4 of neoadjuvant therapy
  • cDNA composition [ Time Frame: at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment ]
    The composition of cDNA in blood samples will be measured
Original Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Health-related quality of life using EORTC QBL-BR-23 scale [ Time Frame: 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 ]
    Assessment of quality of life questions during the past week or during the past 4 weeks (depending on the questions) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
  • Health-related quality of life using EQ5D-5L scale [ Time Frame: 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 ]
    • questions about "self care", "usual activities", "pain /discomfort", anxiety/depression" are assessed on a 5 level-scale using tick boxes : "I have no problem"; "I have slight problems"; "I have moderate problems"; "I have severe problems" "I am unable"
    • assessment of the patient health (good or bad) is measured on a scale numbered from 0 to 100 (100 means the best heath and 0 means the worst)
  • Health-related quality of life using EORTC QLQ-C30 scale [ Time Frame: 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 ]
    • Assessment of quality of life questions (activities, breath, pain, sleep, appetite, vomiting, constipation, others..) are measured on a 4 level-scale: 1 (not at all); 2 (a little); 3 (quite a bit); 4 (very much)
    • Assessment of Overall health and overall quality of life during the past week is measured on a 7 level-scale going from 1 (very poor) to 7 (excellent)
  • Tumor size reduction by mammography [ Time Frame: at screening visit and 12 weeks after start of therapy treatment ]
    The diameters of the tumors in the breast will be measured in millimeter by mammography as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
  • Tumor size reduction by palpation and ultrasound [ Time Frame: at screening visit and 4, 7 and 13 weeks after start of therapy treatment ]
    The diameters of the tumors in the breast will be measured in millimeter by palpation and ultrasound as part of clinical response measure. The tumor size measurement 13 weeks after start of therapy is also used to reach a secondary endpoint: near pCR, defined as tumor sized ypT1a/is, any ypN with tumor size.
  • Overall survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months ]
    The overall survival is defined as time (days) between study treatment allocation and death of patient due to any cause.
  • Duration of invasive disease-free survival [ Time Frame: 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) ]
    Duration of invasive disease-free survival is defined as time (days) between study treatment allocation and relapse, secondary tumor event or death.
  • Number of mastectomies [ Time Frame: 14 weeks after start of therapy treatment ]
    The number of mastectomies will be determined at time of surgery (week 14 and week 18)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE
  • Drug: 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.)
    Other Name: Pertuzumab
  • 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.)
    Other Name: Trastuzumab
  • Drug: Tamoxifen
    20 mg per day for a total of 40 weeks in the adjuvant therapy phase.
  • 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.
  • Drug: Epirubicin
    12 weeks (4cycles) of max. 90mg/sqm in adjuvant therapy phase
  • 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
  • Drug: Anastrozole
    1mg per day for a total of 40 weeks in adjuvant therapy phase
  • Drug: Letrozole
    2,5 mg/day for a total of 40 weeks in adjuvant therapy phase
  • Drug: Exemestane
    25mg/day for a total of 40 weeks in adjuvant therapy phase
  • 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.
  • 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.
  • 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
  • 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
  • Drug: Exemestane
    25mg/day for 12 weeks in neoadjuvant therapy phase; 25mg/day for a total of 40 weeks max. in adjuvant therapy phase
  • 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
  • Drug: Tamoxifen
    20mg per day (given over 12 weeks in the neoadjuvant therapy phase and over 40 weeks max. in the adjuvant therapy phase.
  • 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).
  • 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).
  • Diagnostic Test: Biopsy
    Core biopsy at screening (outside of protocol), at week 4 after randomization, (at week 14 in addition if neoadjuvant phase is prolonged)
  • Procedure: Surgery
    Surgery at week 14 after randomization (or later, if neoadjuvant phase is prolonged)
Study Arms  ICMJE
  • Active Comparator: Paclitaxel+Trastuzumab+Pertuzumab

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

    Adjuvant Therapy: Standard of care

    Interventions:
    • 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
  • Experimental: Endocrine+Trastuzumab+Pertuzumab

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

    Adjuvant Therapy: Standard of care

    Interventions:
    • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 16, 2019)		 257
Original Estimated Enrollment  ICMJE
 (submitted: September 1, 2017)		 259
Actual Study Completion Date  ICMJE March 4, 2024
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03272477
Other Study ID Numbers  ICMJE PH002-TP-II
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Palleos Healthcare GmbH
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Palleos Healthcare GmbH
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Roche Pharma AG
  • WSG WOMEN´S HEALTHCARE STUDY GROUP
  • Cankado GmbH
Investigators  ICMJE
Study Director: Iris Reiser, PhD Palleos Healthcare GmbH
PRS Account Palleos Healthcare GmbH
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP