Pre Operative Trastuzumab in Operable Breast Cancer

November 20, 2023 updated by: Dr Rajendra A. Badwe

A Phase III Double Blind Randomized Placebo Controlled Study of Trastuzumab as Short Duration Preoperative Therapy in Patients With HER2-neu Positive Operable Breast Cancer

Background Information and Rationale:

Trastuzumab is a humanized monoclonal antibody that acts extracellularly on the erbB-2 receptor.Trastuzumab is a recombinant humanized IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2/erbB-2),which has shown in both in vitro assays and in animals, to inhibit the proliferation of human tumour cells that overexpress erbB-2. Additionally, trastuzumab is a potent mediator of antibody-dependent cell-mediated cytotoxicity (ADCC). In vitro, trastuzumab-mediated ADCC has been shown to be preferentially exerted on erbB-2 overexpressing cancer cells compared with cancer cells that do not overexpress erbB-2. Trastuzumab has emerged as a widely accepted standard of care for erbB-2-positive disease. (Metastatic/ adjuvant/neoadjuvant.

Our current hypothesis suggests that the cells which are disseminated at the time of surgery will encounter an inhospitable environment which will be anti-HER in nature. Therefore combining the above mentioned streams of thought, we would like to assess the effect of a short pre-operative course of Trastuzumab on breast cancer relapse. The study is proposed in HER2 positive patients with operable breast cancer.

Objectives :

Primary:

The primary objective of the study is to see the effect of short duration of peri-operative Trastuzumab on disease-free survival in comparison in all patients

Secondary:

The safety of the pre-operative therapies including the early post operative morbidity

  1. Overall survival (OS) in all patients and in pathologically node positive patients.
  2. The level of circulating tumor cells (CTCs) in the peripheral blood assessed before starting pre-operative therapy and at the same time point in the control arm, level of CTCs 10 minutes prior to start of surgery, during surgery and 10 days after surgery on 40 consecutive consenting patients (20 in each arm). The levels of circulating chromatin will also be estimated at the same time points as CTC for these 40 patients.
  3. Evaluation of the paraffin blocks for pTEN loss6-8 and p95ErbB2 truncated form of HER2 on 100 consecutive consenting patients (50 in each arm).9-11

Study Design :

This is phase 3, randomized Double blinded parallel group study of Trastuzumab in pre operative setting in operable breast cancer patients.

Approximately 1000 patients with Women with HER2neu positive, T1/T2/T3 and N0/N1. clinical T4 and/or N2 disease who are considered operable by the treating surgeon with histopathological diagnosis on core biopsies, will be included in the study. Patients with T4 or N2 (locally advanced and large operable for neo-adjuvant chemotherapy) will not be included. All node positive patients will receive single injection of Depot Inj. Progesterone 500 mg deep IM 4 -14 days prior to surgery

Patients will be stratified, before randomization for Tumor size, menopausal status, and affordability for Trastuzumab and centre of the study. These patients will then be randomized 1:1 to receive the following

Intervention arm: .A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute intravenous infusion in 250 ml of normal saline, in the window period of 10-15 4 to 14 days (both days inclusive) prior to the planned date of surgery.

Control arm: A 90 minute intravenous infusion of saline as placebo

All patients will thereafter receive standard post-operative adjuvant therapy as per local institutional practice including hormonal therapy, chemotherapy and radiation therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

1100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Rajendra A Badwe, MS
  • Phone Number: 4265 91-22-21477000
  • Email: badwera@gmail.com

Study Locations

  • India
      • Mumbai, India, 400012
        • Recruiting
        • Tata Memorial Centre
        • Principal Investigator:
          • Rajendra A Badwe, MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:a.

  1. Female subjects aged 18 years or older.
  2. Histologically and/or cytologically confirmed diagnosis of breast cancer. Clinical stages breast cancer: HER2 positive, T1 or T2 or T3, N0 or N1, resectable T4, or resectable N2, (all M0)
  3. Documentation of erbB-2 gene amplification by FISH (as defined by a ratio >2.2) or chromogenic in situ hybridization (CISH, as defined by the manufacturer's kit instruction) or documentation of erbB-2-overexpression by IHC (defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local laboratory.
  4. LVEF within institutional range of normal as measured by MUGA or ECHO.

  5. Screening laboratory values within the following parameters:

    1. Absolute neutrophil count (ANC) ≥1.5 x 109 /L (1500/mm3)
    2. Platelet count ≥100 x 109/L (100,000/mm3)
    3. Hemoglobin ≥9.0 g/dL (90 g/L)
    4. Serum creatinine ≤1.5 x upper limit of normal (ULN)

    5. Total bilirubin ≤1.5 x ULN (<3 ULN if Gilbert's disease) 6Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)

      • 2.5 x ULN

Exclusion Criteria:

  1. Bilateral breast cancer
  2. Active uncontrolled cardiac disease, including cardiomyopathy, CHF (New York Heart Association [NYHA] functional classification of ≥3), unstable angina, and myocardial infarction (within 12 months of study entry).
  3. Inadequately controlled hypertension (ie, systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg).
  4. Family history of congenital long or short QT syndrome, Brugada syndrome or QT/QTc interval > 0.45 second or known history of QT/QTc prolongation or torsade de pointe (TdP).
  5. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or grade ≥2 diarrhea of any etiology at baseline).
  6. Women who are pregnant, breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug Trastuzumab
A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute infusion in 250 ml of normal saline, in the window period of 14 days (both days inclusive) prior to the planned date of surgery.
Drug: Trastuzumab
A single dose of Trastuzumab (Herceptin, Hoffman La Roche) at 8 mg/Kg as a 90 minute infusion in 250 ml of normal saline, in the window period of 14 days (both days inclusive) prior to the planned date of surgery.
Other Names:
  • Herceptin
Placebo Comparator: Control
A 90 minute intravenous infusion of saline as placebo
Drug: Placebo
A 90 minute intravenous infusion of saline as placebo
Other Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival
Time Frame: up to 5 yrs

Survival follow-up visits (or information Collected via telephone call) will be conducted approximately every 6 months (ie, 24 weeks) starting from the last day of primary (adjuvant) treatment.

The subject will be called at clinic and will be carefully examined by a member of study team. A mammogram will be done every 18 months. If patient is symptomatic,additional investigations will be performed. Subject status as alive, alive with disease will be documented in the source file.
up to 5 yrs

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 5 yrs
4.1.1. Overall survival (OS) in all patients and in pathologically node positive patients.
Up to 5 yrs
Circulating Tumour Cells in Peripheral Blood
Time Frame: 1. before starting pre-operative therapy and at the same time point in the control arm. 2. 10 minutes prior to start of surgery. 3. During surgery . 4. 10 days after surgery
1. before starting pre-operative therapy and at the same time point in the control arm. 2. 10 minutes prior to start of surgery. 3. During surgery . 4. 10 days after surgery
4.1.3. Evaluation of the paraffin blocks for pTEN loss6-8 and p95ErbB2 truncated form of HER2
Time Frame: upto 5 yrs
upto 5 yrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr Rajendra A. Badwe

Collaborators

Tata Memorial Hospital

Investigators

  • Principal Investigator: Rajendra A Badwe, MS, Director and professor, Surgical Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 1, 2013

First Submitted That Met QC Criteria

February 6, 2013

First Posted (Estimated)

February 7, 2013

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TMH Project-982

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HER2 Positive Breast Cancer

Clinical Trials on Trastuzumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Egypt

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe