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A clinical study to compare the efficacy, safety and immunogencity of two formulations of trastuzumab in women with HER2 Positive Early breast cancer.

Phase 3
Completed
Conditions
Malignant neoplasm of breast of unspecified site,
Registration Number
CTRI/2019/01/017029
Lead Sponsor
Tanvex Biologics Corp
Brief Summary

This is a randomized, double-blinded, parallel group, equivalence, multicenter Phase III study. The purpose of this study is to compare the research medicine TX05 with the medicine Herceptin® on how effective they are and how well are tolerated, to find out which one is better for treating HER2+ EBC. TX05 has been designed to be a “biosimilar productâ€, which means, TX05 has the same active ingredient as Herceptin®. The active ingredient is called trastuzumab, which blocks HER2 protein. Thus, similar effects as Herceptin® are expected in patients taking TX05. However this has not yet been proven. The study will also measure the amount of TX05 or Herceptin® in your body and whether or not your body makes antibodies against TX05 or Herceptin®. Antibodies against TX05 could reduce the amount of the TX05 in the blood and its effects on your cancer. Herceptin® is approved for use by Drugs Controller General of India (DCGI), the health authority that gives approval for new medicines to be prescribed in India.

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Female
Target Recruitment
800
Inclusion Criteria
    1. Signed written informed consent. 2. Females ≥ 18 years of age. 3. Histologically confirmed HER2 overexpressing invasive primary operable Stage II/IIIa breast cancer by American Joint Committee on Cancer 7th Edition staging criteria. Tumor tissue sample must be available for central analysis. 4. Planned surgical resection of breast tumor (lumpectomy or mastectomy, and SN biopsy or ALND). 5. Planned neoadjuvant chemotherapy. 6. HER2 overexpression as assessed by:.
  • Gene amplification by fluorescent in-situ hybridization (FISH), chromogenic in-situ hybridization (CISH), or dual in-situ hybridization (DISH) (as defined by the manufacturer’s kit instruction); OR.
  • Overexpression by immunohistochemistry (IHC) categorized as IHC 3+; OR.
  • Overexpression by immunohistochemistry categorized as IHC2+ with FISH, CISH, or DISH confirmation. 7. Ipsilateral, measurable tumor longest diameter > 2 cm. 8. Known estrogen receptor (ER) and progesterone receptor (PR) hormone status prior to randomization. If ER/PR status is not available locally, testing may be performed by central laboratory during Screening. 9. ECOG performance status of 0 or 1. 10. Adequate bone marrow, hepatic, and renal functions as evidenced by the following:.
  • Absolute neutrophils count ≥ 1,500/μL.
  • Hemoglobin ≥ 9 g/dL.
  • Platelet count ≥ 100,000/μL.
  • Creatinine clearance ≥ 40 mL/min.
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
  • Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 x ULN.
  • Alkaline phosphatase ≤ 5 x ULN 11. LVEF ≥ 50% or within the normal level of the institution, as assessed by echocardiography or MUGA scan. 12. Able to comply with the study protocol. 13. Female subjects of childbearing potential must have a negative serum pregnancy test within 1 week of first administration of study drug and agree to use effective contraception (hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide) throughout the study period and for 6 months after last administration of study drug.
Exclusion Criteria
    1. Participation in any interventional clinical study or having taken any investigational therapy during the 2 month period immediately preceding administration of the first dose of study drug. 2. Bilateral breast cancer. 3. Inflammatory breast cancer. 4. Metastases. 5. Previous chemotherapy, biologic therapy, radiation, or surgery for any active malignancy, including breast cancer. 6. Subjects with one or more of the following conditions:.
  • Cardiac insufficiency (New York Heart Association III or IV); myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable angina pectoris, uncontrolled arrhythmia, or pulmonary embolus within the previous 12 months prior to the first administration of study drug.
  • Clinically significant active infection.
  • Poorly controlled diabetes mellitus.
  • Uncontrolled hypertension (blood pressure > 150/100 mmHg despite optimal medical therapy).
  • Major surgery, significant traumatic injury, or radiation therapy within 4 weeks of first administration of study drug.
  • Grade 3 hemorrhage within 4 weeks of first administration of study drug. 7. Pre-existing clinically significant (≥ Grade 2) peripheral neuropathy. 8. History of malignancy within the last 5 years, except adequately excised squamous or basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer. 9. Severe dyspnea at rest requiring supplementary oxygen therapy.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To demonstrate the therapeutic equivalence of TX05(biosimilar of Trastuzumab) to Herceptin based on the pCR rate following neoadjuvant chemotherapy,defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapyThe study will consist of a Screening period (Days -28 to 0), and 8 cycles of neoadjuvant treatment (Week 0 [Day 1] to Week 24), followed by surgery (3 to 7 weeks from the 1st day of the last cycle/last dose of study drug).
(ypT0/Tis ypN0), in subjects with human epidermal growth factor receptor positive (HER2+) invasive earlyThe study will consist of a Screening period (Days -28 to 0), and 8 cycles of neoadjuvant treatment (Week 0 [Day 1] to Week 24), followed by surgery (3 to 7 weeks from the 1st day of the last cycle/last dose of study drug).
breast cancer.The study will consist of a Screening period (Days -28 to 0), and 8 cycles of neoadjuvant treatment (Week 0 [Day 1] to Week 24), followed by surgery (3 to 7 weeks from the 1st day of the last cycle/last dose of study drug).
Secondary Outcome Measures
NameTimeMethod
To compare objective response rate (ORR) between the 2 treatment arms;immunogenicity, safety, and tolerability will also be assessed.ORR, according to RECIST version 1.1, as assessed by the

Trial Locations

Locations (31)

Deenanath Mangeshkar Hospital & Research Center

🇮🇳

Pune, MAHARASHTRA, India

Acharya Tulsi Cancer Regional Cancer Treatment & Research Institute

🇮🇳

Bikaner, RAJASTHAN, India

Apollo Speciality Hospital

🇮🇳

Chennai, TAMIL NADU, India

Artemis Hospitals - Artemis Cancer Centre

🇮🇳

Gurgaon, HARYANA, India

Basavatarakam Indo American Cancer Hospital & Research Institute

🇮🇳

Hyderabad, TELANGANA, India

Bhagwan Mahaveer Cancer Hospital & Research Centre

🇮🇳

Jaipur, RAJASTHAN, India

Chopda Medicare & Research Center Pvt Ltd, Magnum Heart Institute

🇮🇳

Nashik, MAHARASHTRA, India

City Cancer Center

🇮🇳

Krishna, ANDHRA PRADESH, India

Deep Hospital

🇮🇳

Ludhiana, PUNJAB, India

Department of Radiotherapy and Oncology,Shirdi Sai Baba Cancer Hospital & Research Centre

🇮🇳

Udupi, KARNATAKA, India

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Deenanath Mangeshkar Hospital & Research Center
🇮🇳Pune, MAHARASHTRA, India
Dr Sachin Sharadchandra Hingmire
Principal investigator
0091-9324517648
sshingmire@yahoo.com

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