Clinical Trial Details (PDF Generation Date :- Sat, 21 Jul 2018 20:30:11 GMT) CTRI Number Last Modified On 11/04/2016 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2014/07/004786 [Registered on: 30/07/2014] - Trial Registered Prospectively Interventional Drug Biological Randomized, Parallel Group, Active Controlled Trial A Study of PF-05280014 [Trastuzumab-Pfizer] or Herceptin [Trastuzumab-EU] Plus Paclitaxel in HER2 Positive First Line Metastatic Breast Cancer Treatment A phase 3 randomized, double-blind study of PF-05280014 plus paclitaxel versus trastuzumab plus paclitaxel for the first-line treatment of patients with HER2-positive metastatic breast cancer Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) B3271002, Protocol Amendment 1, dated 29 Jul 2013 NCT01989676 Designation Affiliation Phone Fax Email Designation Affiliation Protocol Number ClinicalTrials.gov Details of Principal Investigator Swapnali Raut Director Compliance Oversight Pfizer Limited Pfizer Centre, Patel Estate, SV Road, Jogeshwari West Mumbai 400102 Swapnali.Raut@pfizer.com Details Contact Person (Scientific Query) Swapnali Raut Director Compliance Oversight Pfizer Limited Pfizer Centre, Patel Estate, SV Road, Jogeshwari West Details Contact Person (Public Query) Phone Fax Email Designation Affiliation 400102 Swapnali.Raut@pfizer.com Details Contact Person (Public Query) Swapnali Raut Director Compliance Oversight Pfizer Limited Pfizer Centre, Patel Estate, SV Road, Jogeshwari West 400102 page 1 / 8
Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Phone Fax Email Swapnali.Raut@pfizer.com Source of Monetary or Material Support > Pfizer Inc, 235 East 42nd Street, New York, NY 10017, United States of America Type of Sponsor NIL List of Countries Argentina Brazil Chile Czech Republic Greece Hungary Japan Mexico Peru Philippines Poland Portugal Republic of Korea Romania Russian Federation Serbia South Africa Spain Thailand Turkey Ukraine United States of America of Principal Investigator Dr Surendra Nath Senapati Primary Sponsor Details Pfizer Limited The Capital, 1802/1901, Plot. C-70, G Block, Bandra Kurla Complex, Bandra (East), Mumbai 400051, Maharashtra, Pharmaceutical industry-global of Site Site Phone/Fax/Email Acharya Harihar Regional Cancer Centre Department of Radiation Oncology,Room no 1, Acharya Harihar Regional Cancer Centre, Medical Road, Mangalabag, Cuttack - 753007, Odisha, Cuttack ORISSA 09437031718 06712304444 snsenapati2007@gmail.com Dr Ravi Mohan Andhra Medical Department of Medicine 09849123463 page 2 / 8
Pedapenki Dr Sachin Sharadchandra Hingmire College, King George Hospital Deenanath Mangeshkar Hospital & Research Centre Dr Donald J Fernandes Manipal Centre for Clinical Research, Kasturba Hospital New Block, Andhra Medical College, King George Hospital, Visakhapatnam 530002, Andhra Pradesh, Visakhapatnam ANDHRA PRADESH Basement, D WING, Oncology Research Room no. 12, Oncology Research, Erandawane, Pune 411004, Maharashtra, Pune Department of Radiotherapy and Oncology, Mezzanine Floor, Room 32, Manipal Centre for Clinical Research, Kasturba Hospital, Post Box. 7, Manipal University, Manipal - 576104, Karnataka, Udupi KARNATAKA Dr Poonam Patil Manipal Hospital Dept of Oncology,Ground floor, Room 3, 98, HAL Airport Road, Bangalore 560017, Karnataka, Bangalore KARNATAKA Dr Kirushna Kumar Kosanam Subramanian Dr Sachin Vamanrao Almel Dr Tushar Vishvasrao Patil Meenakshi Mission Hospital and Research Centre P. D. Hinduja National Hospital & Medical Research Centre Sahyadri Speciality Hospital Ground floor, Department of Medical Oncology, Lake Area, Melur Road, Madurai - 625107, Tamil Nadu, Madurai TAMIL NADU Room no 106, Ground Floor, Dept of Oncology, Veer Savarkar Marg, Mahim, Mumbai - 400016, Maharashtra, Mumbai Department of oncology, Room no.114, 1st floor, 30C, Erandwane, Karve Road, Pune - 411004, Maharashtra, 08912714644 oncoravi@rediffmail.co m 09324517648 02066023071 sshingmire@yahoo.co m 09448252735 08202571651 donaldjf@yahoo.com 09945687185 08025207181 poonampatil@yahoo.co m 09787713004 04522586353 drkskk@yahoo.com 09820229481 02224440425 sachinalmel@gmail.co m 09552522556 02025459117 tushar.patil@sahyadrih ospitals.com page 3 / 8
Details of Ethics Committee Regulatory Clearance Status from DCGI Health Condition / Problems Studied Dr Shailesh Arjun Bondarde Shatabdi Super Speciality Hospital Pune Dept of Oncology, Room no. 4, Suyojit City Centre, Opposite Mahamarg Bus Stand, Mumbai Naka, Nashik - 422005, Maharashtra, Nashik Dr Jaya Ghosh Tata Memorial Hospital Dept of Medical oncology, Room no. 1103, Dr. E. Borges Road, Parel, Mumbai - 400012, Maharashtra, Mumbai 09822012427 02532502105 shaileshbondarde1971 @gmail.com 09769997881 02224177201 archana_jaya_ghosh@ yahoo.co.in of Committee Approval Status Date of Approval Is Independent Ethics Committee? Acharya Harihar Regional Cancer Centre Institutional (AHRCC-IEC), of Manipal Hospitals (ECMH) Institutional Ethics Committee (IEC),(DMHRC), Institutional Ethics Committee, King George Hospital Institutional Ethics Committee, P. D. Hinduja Hospital & RC Institutional Ethics Committee, Tata Memorial Hospital Manipal University Meenakshi Mission Hospital & Research Centre Institutional Sahyadri Hospitals Ltd Shatabdi Hospital (SHEC), Status Approved 07/01/2014 Submittted/Under Review Date Specified Approved 21/02/2014 Approved 23/12/2013 Submittted/Under Review Submittted/Under Review Date Specified Date Specified Approved 12/12/2013 Approved 03/02/2014 Approved 30/01/2014 Submittted/Under Review Date Specified Date Approved/Obtained 24/07/2014 Health Type Patients Condition Metastatic Breast Cancer page 4 / 8
Intervention / Comparator Agent Type Details Intervention PF-05280014 On treatment days when both PF-05280014 and paclitaxel are administered, the order of administration should be PF-05280014 infusion, followed by paclitaxel infusion. During the period in which PF-05280014 is administered in combination with paclitaxel, and until at least Week 33 of the study, PF-05280014 will be administered in a weekly regimen on Days 1, 8, 15 and 22 of each 28-day cycle. The first administration on Day 1, Cycle 1 will be a loading dose of 4 mg/kg infused over 90 minutes. Subsequent weekly infusions will be 2 mg/kg administered over 30 to 90 minutes depending on tolerability. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Treatment of individual patients with PF-05280014 well beyond Week 53 of the study is expected to be common. Intervention Paclitaxel Paclitaxel will be administered in a weekly regimen, on Days 1, 8 and 15 of each 28-day cycle (ie, no paclitaxel is administered on Day 22 of each cycle). The starting dose of paclitaxel will be 80 mg/m2 by IV infusion over 60 minutes. Depending on observed toxicity attributed to paclitaxel, provision is made for dose reduction to 70 mg/m2 and then 60 mg/m2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained. Comparator Agent Herceptin On treatment days when both trastuzumab and paclitaxel are administered, the order of page 5 / 8
Inclusion Criteria administration should be trastuzumab infusion, followed by paclitaxel infusion. During the period in which trastuzumab is administered in combination with paclitaxel, and until at least Week 33 of the study, trastuzumab will be administered in a weekly regimen on Days 1, 8, 15 and 22 of each 28-day cycle. The first administration on Day 1, Cycle 1 will be a loading dose of 4 mg/kg infused over 90 minutes. Subsequent weekly infusions will be 2 mg/kg administered over 30 to 90 minutes depending on tolerability. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzumab regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Treatment of individual patients with trastuzumab well beyond Week 53 of the study is expected to be common. Comparator Agent Paclitaxel Paclitaxel will be administered in a weekly regimen, on Days 1, 8 and 15 of each 28-day cycle (ie, no paclitaxel is administered on Day 22 of each cycle). The starting dose of paclitaxel will be 80 mg/m2 by IV infusion over 60 minutes. Depending on observed toxicity attributed to paclitaxel, provision is made for dose reduction to 70 mg/m2 and then 60 mg/m2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained. Age From Age To Gender Details 18.00 Year(s) 99.00 Year(s) Female Inclusion Criteria Female patients aged 18 years or older. Histologically confirmed diagnosis of breast cancer. page 6 / 8
Presence of metastatic disease. Prior documentation of HER2 gene amplification or overexpression. Determination of HER2 positive status using one of the Sponsor accepted analytical test. Available tumor tissue for central review of HER2 status. At least 1 measurable lesion as defined by RECIST 1.1. Eastern Cooperative Oncology Group status of 0 to 2. Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan. Exclusion Criteria Details Exclusion Criteria Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment. Prior systemic therapy for metastatic disease (except endocrine therapy). Prior cumulative dose of doxorubicin of more than 400 mg per m2, epirubicin dose more than 800 mg per m2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mgper m2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg per m2 of doxorubicin. Inflammatory breast cancer. Active uncontrolled or symptomatic central nervous system metastases. Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Centralized Participant, Investigator and Outcome Assessor Blinded Primary Outcome Outcome Timepoints Percentage of Participants With Objective Week 25 Response Rate (ORR) The percent of patients within each treatment group that achieved Complete Response (CR) or Partial Response (PR) by Week 25 of the study (window ± 14 days) and confirmed on a follow-up assessment, in accordance with the RECIST 1.1. Secondary Outcome Outcome Timepoints Duration of Response (DOR) up to 12 months The time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of Progressive Disease (PD) or to death due to any cause in the absence of documented PD. 1-year Progression-Free Survival (PFS) Rate The time from date of randomization to first progression of disease (PD) or death due to any cause in the absence of documented PD. up to 12 months 1-year Survival Rate Time from date of randomization to death due to any cause while the patient is on the study. up to 12 months page 7 / 8
Powered by TCPDF (www.tcpdf.org) PDF of Trial Maximum Observed Plasma Concentration (Cmax) Peak PF-05280014 and trastuzumab-eu concentrations at selected cycles. up to 4 months Minimum Observed Plasma Trough Concentration (Cmin) Trough PF-05280014 and trastuzumab-eu concentrations at selected cycles. up to 24 months Incidence of ADA The percentage of patients with positive ADA and neutralizing antibodies will be summarized for each treatment arm. up to 24 months Target Sample Size Phase of Trial Phase 3 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Total Sample Size=690 Sample Size from =65 01/08/2014 25/02/2014 Years=3 Months=2 Days=0 Open to Recruitment t Yet Recruiting The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-eu) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-eu. page 8 / 8