Trastuzumab (Herclon) labelled with Radioisotope for HER2 positive metastatic breast cancer
- Conditions
- Health Condition 1: C50- Malignant neoplasm of breastHealth Condition 2: C50-C50- Malignant neoplasms of breast
- Registration Number
- CTRI/2018/09/015755
- Lead Sponsor
- Intramural Tata Memorial Centre
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Inclusion criteria (all of the following)
a) Age more than 18 years and less than equal to 70 years.
b) Signed, written informed consent (approved by the Institutional Ethics Committee [IEC]), prior to any study procedure.
c) Histologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative section.
d) Male or female patient with documented HER2 positive [defined as either 3 plus by immunohistochemistry or with evidence of gene amplification (more than 2.0) by fluorescence in situ hybridization (FISH) breast cancer].
e) Patients with at least 1 measurable or evaluable lesion as per RECIST criteria 1.1 and showing FDG uptake on a FDG PETCT plus CECT study.
f) Patients with metastatic breast cancer who have received at least 1 line of treatment (with or without HER2 targeted therapy) in the metastatic setting and have shown disease progression after the treatment and have received one line of neo (adjuvant) chemotherapy (with or without HER2 targeted therapy). Thus patient should have received at least 2 lines of chemotherapy including the neo (adjuvant) one.
g) Eastern Cooperative Oncology Group (ECOG) performance status(PS) 2 or less.
h) Known or documented LVEF of 50 percent or greater
i) Adequate organ function as determined by the following Laboratory results:
i. Hemoglobin more than equal to 9 Grams Per Decilitre
ii. Platelet Count more than equal to 100,000 x 10e9 per liter
iii. Serum Creatinine less than equal to 1.1 milligram per deciliter x 1.5 times of upper limit
iv. Aspartate aminotransferase (SGOT [AST] or Alanine aminotransferase (SGPT)[ALT]) less than equal to 2.5 times the upper limit of institutional normal values. or less than equal to 5 x ULN in presence of liver metastases.
j) A negative serum β-HCG test for women of childbearing potential (premenopausal, or less than 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization [i.e., absence of ovaries and or uterus]).
Exclusion criteria
a) Patients who have received trastuzumab in the preceding 30 days prior to date of 1st study treatment.
b) Patients showing absence of FDG uptake on the FDG PETCT plus CECT scan.
c) Previous Grade 3 or higher allergic reaction to trastuzumab that resulted in discontinuation of trastuzumab therapy
d) Patients who had received extensive radiotherapy (defined as radiation to more than 50 percent of marrow space) this is likely to compromise the marrow reserve.
e) Active autoimmune or history of autoimmune disease.
f) Pregnant and lactating women.
g) Patients who are unable to lie in supine position.
h) Patients with no 177Lu Trastuzumab uptake in any target lesion on dosimetric study.
i) Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
j) Brain Metastasis.
k) Positive for human immunodeficiency virus (HIV) infection.
l) History of congestive heart failure of any New York Heart Association (NYHA) class.
m) Clinically significant valvular heart disease or uncontrollable high-risk cardiac arrhythmia.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary outcome measures <br/ ><br>a) Correlation of tumor uptake on 177Lu trastuzumab scintigraphy with 18F FDG uptake on PETCT plus CECT SCAN. <br/ ><br>b) To determine the pharmacokinetic profile of the 177Lu trastuzumab radiotracer. <br/ ><br>c) To quantify the fraction of patients who could benefit from therapeutic dose of 177Lu Trastuzumab based on dosimetric imaging study. <br/ ><br> <br/ ><br>Timepoint: 12 months from inclusion of last patient
- Secondary Outcome Measures
Name Time Method Secondary outcome measures <br/ ><br>a) The primary end point will be RECIST1.1 defined tumor response in the target lesions at the interval of eight weeks (plus-minus 1 week) from the last dose of 177Lu Trastuzumab. <br/ ><br>b)b) To evaluate safety, the fraction of the patients experiencing grade III or higher toxicity (CTCAE 4.03). Cardiac toxicity as defined by fall of LVEF to less than 50 percent if the initial LVEF was more than 50 percent or fall of more than 10 percent from baseline value. <br/ ><br>Timepoint: 12 months from inclusion of last patient