A randomized, double-blind, parallel group, Phase III trial to compare the efficacy, safety, and immunogenicity of TX05 with Herceptin® in subjects with HER2 positive early breast cancer
- Conditions
- -C50 Malignant neoplasm of breastMalignant neoplasm of breastC50
- Registration Number
- PER-027-18
- Lead Sponsor
- Tanvex Biologics Corporation,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 88
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.
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.
10.Known positive status for human immunodeficiency virus.
11.Known acute or chronic-active infection with hepatitis B surface antigen or hepatitis C virus.
12.History or presence of a medical condition or disease that in the investigator´s opinion would place the subject at an unacceptable risk for study participation.
13.Lactating or pregnant female.
14.Women of childbearing potential who do not consent to use highly effective methods of birth control (e.g. true abstinence [periodic abstinence {e.g. calendar ovulation, symptothermal, post-ovulation methods} and withdrawal are not acceptable methods of contraception], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 6 months after the last administration of study drug. Subjects must agree to not breast-feed while receiving study drug.
15.Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products, trastuzumab, murine proteins, or to any of the excipients.
16.Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range despite optimal medical therapy.
17.Subject likely to not be available to complete all protocol required study visits or procedures.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Primary efficacy endpoint: the proportion of subjects<br>in each treatment arm who, based on the central pathological<br>review, achieve pCR, defined as the absence of residual<br>invasive cancer on hematoxylin and eosin evaluation of the<br>complete resected breast specimen and all sampled regional<br>lymph nodes following completion of neoadjuvant systemic<br>therapy (ypT0/Tis ypN0). Pathology of the tumor sample and<br>pathologic response will be assessed locally and reviewed<br>centrally by a qualified pathologist. The primary efficacy<br>analysis will be based on the central pathological review<br>Measure:Efficacy Endpoints<br>Timepoints:week N° 28<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Defined as the percentage of subjects having Complete or Partial Response at the EOT/ET Visit, according to RECIST version 1.1 (see Appendix 4), as assessed by the investigator.<br><br>Frequency and percentage of subjects who meet<br>the pCR and ORR criteria will be reported. Risk<br>Ratio and its 95% CI will be estimated. Analysis<br>will be performed with the mITT population and<br>sensitive analysis will be performed with the PP<br>population.<br>Detailed analysis will be described in the SAP.<br>Measure:To compare objetive response rate (ORR) between the 2 treatment arms; immunogenicity, safety, and tolerability will also be assessed.<br>Timepoints:Week N° 6<br>