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Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in Patients With HER2-positive Breast Cancer (IMMUN-HER)

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ClinicalTrials.gov Identifier: NCT03144947
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : February 27, 2019
Sponsor:
Collaborators:
University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit
University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology
University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione
Clirest s.r.l.
Mipharm SpA
Arithmos srl
Temas srl
Information provided by (Responsible Party):
Gruppo Oncologico Italiano di Ricerca Clinica

Tracking Information
First Submitted Date  ICMJE April 7, 2017
First Posted Date  ICMJE May 9, 2017
Last Update Posted Date February 27, 2019
Actual Study Start Date  ICMJE November 29, 2016
Estimated Primary Completion Date March 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph) [ Time Frame: 6 months after last patient in ]
stromal lymphocytes will be scored quantitatively on H&E stained whole-tumor slides as a continuous variable expressed as stromal percentage area within the tumor boundaries. For tumors with heterogeneous TILs, median values will be calculated from multiple counts from different tumor areas. Intra-epithelial TILs will also be recorded as well as tertiary lymphoid structures. Tumor regression will be scored based on recommended criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03144947 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Associations between biomarkers (TIL, Tumor specific lymphocyte cell activity (TLA), and Fc-gamma-R polymorphisms) and between each biomarker with clinical outcome variables. [ Time Frame: at baseline, 6 months and 5 years after last patient in ]
  • Frequency of toxicity Events: frequency of moderate and severe toxicity events and drop-out rate due to theraphy related toxicity (NCICommon Toxicity Criteria v 4.0) [ Time Frame: 3.5 years ]
  • HRQOL during study treatment based on FACT-B [ Time Frame: at baseline, and 6 months after last patient in ]
    mean FACT-B scores assessed at enrolment and mean FACT-B scores assessed before surgery.
  • Complete pathological response rate by treatment arm [ Time Frame: 6 months after last patient in ]
  • 5-year disease-free survival by treatment arm between treatment arms [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Trastuzumab in Patients With HER2-positive Breast Cancer
Official Title  ICMJE Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients With Operable or Locally Advanced/Inflammatory HER2-positive Breast Cancer (ImmunHER)
Brief Summary Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients with Operable or Locally Advanced /Inflammatory HER2-positive Breast Cancer (ImmunHER)
Detailed Description Women with histologically confirmed HER2-positive breast cancer with locally advanced, inflammatory,or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Non comparative, multi-center, open-label, neoadjuvant, randomized study, the purpose of randomization is to reduce bias owing to patient selection into treatments groups.
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Cancer, Breast
Intervention  ICMJE
  • Biological: Trastuzumab IV

    Pre-randomization phase:

    FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2; cyclophosphamide 500 mg/m2) x 3 cycles

    Post-randomization phase:

    Group A: Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

    by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

    *The dose of docetaxel may be escalated to 100 mg/m 2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated. After surgery, study patients will receive trastuzumab x 14 cycles using the same formulation (SC or IV) of the preoperative phase.

    Other Name: Herceptin-150 mg
  • Biological: Trastuzumab SC

    Pre-randomization phase:

    FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2;

    Group B: Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

    *The dose of docetaxel may be escalated to 100 mg/m 2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated. After surgery, study patients will receive trastuzumab x 14 cycles using the same formulation (SC or IV) of the preoperative phase.

    Other Name: Herceptin-600 mg/5 mL
  • Biological: Pertuzumab
    pertuzumab IV (840 mg loading dose, followed by 420 mg) weeks for 4 cycles (both arms)
    Other Name: PerJeta 420 mg
  • Drug: Docetaxel
    docetaxel (75 mg/m2), every 3 weeks for 4 cycles (both arms). The dose of docetaxel may be escalated to 100 mg/m2 at the investigator's discretion on subsequent cycles if the initial dose is well tolerated.
    Other Name: Docetaxel 20 MG/ML
Study Arms  ICMJE
  • Experimental: Group A

    Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.

    After surgery, study patients will receive trastuzumab IV x 14 cycles

    Interventions:
    • Biological: Trastuzumab IV
    • Biological: Pertuzumab
    • Drug: Docetaxel
  • Experimental: Group B
    Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles. After surgery, study patients will receive trastuzumab SC x 14 cycles
    Interventions:
    • Biological: Trastuzumab SC
    • Biological: Pertuzumab
    • Drug: Docetaxel
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 4, 2017)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date March 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Previously untreated, infiltrating primary breast cancer with locally advanced, inflammatory, or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
  • HER2 positivity (either immunohistochemistry 3+ or fluorescent in situ hybridization amplification).
  • Age 18 or older.
  • Eastern Cooperative Oncology Group performance status of 0 to 1.
  • Availability of tumor tissue for biologic and molecular examination before starting primary treatment.
  • Left ventricular ejection fraction within the institutional range of normal.
  • Normal organ and marrow function.
  • Adequate contraception methods for women of childbearing potential.
  • Prior diagnosis of cancer is allowed as long as patient is free of disease and has been off treatment for the prior malignancy for a minimal interval of 3 years.
  • Written informed consent.

Exclusion Criteria:

  • Either stage I or IV breast cancer.
  • Prior trastuzumab or pertuzumab.
  • Any prior chemotherapy.
  • Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
  • Undergone major surgery (e.g., intrathoracic, intra-abdominal or intra-pelvic) 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery.
  • Breast radiotherapy prior to starting study.
  • Known hypersensitivity to the investigational drugs or any of their excipients.
  • Evidence of any disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an GOIRC-01-2016 ImmunHER Protocol Version 1.0, 11 April 2016 Page 6 of 140 investigational drug, or puts the patient at high risk for treatment-related complications.
  • Moderate/severe hepatic impairment (Child- Pugh B/C).
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Concurrent malignancy or malignancy within 3 years prior to study enrollment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or insitu carcinoma of the uterine cervix.
  • Pregnancy or breastfeeding (breast feeding should be discontinued to be enrolled in the study).
  • Women of childbearing potential that refusal to adopt adequate contraceptive measures.
  • Unwilling or unable to comply with the protocol. -
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03144947
Other Study ID Numbers  ICMJE GOIRC-01-2016
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
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gruppo Oncologico Italiano di Ricerca Clinica
Study Sponsor  ICMJE Gruppo Oncologico Italiano di Ricerca Clinica
Collaborators  ICMJE
  • University Hospital of Parma: Department of Biomedical, Biotechnological and Translational Sciences, Pathological Anatomy and Histology Unit
  • University Hospital of Parma:Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology
  • University Hospital of Parma:Statistica medica ed epidemiologia clinica-UO Ricerca e Innovazione
  • Clirest s.r.l.
  • Mipharm SpA
  • Arithmos srl
  • Temas srl
Investigators  ICMJE Not Provided
PRS Account Gruppo Oncologico Italiano di Ricerca Clinica
Verification Date February 2019

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