CTRI/2015/05/005766 [Registered on: 11/05/2015] Trial Registered Prospectively
Last Modified On:
19/07/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A Study of Pertuzumab in Combination with Trastuzumab and Docetaxel in Treatment of Indian Patients with Her2-positive Breast Cancer.
Scientific Title of Study
ML29282-A PHASE IV, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY OF PERTUZUMAB (IN COMBINATION WITH TRASTUZUMAB AND DOCETAXEL) IN FIRST LINE TREATMENT OF INDIAN PATIENTS WITH HER2-POSITIVE ADVANCED (METASTATIC OR LOCALLY RECURRENT) BREAST CANCER
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ML29282 version 1.0 dated 06 Jun 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sudeep Gupta
Designation
Professor of Medical Oncology
Affiliation
Tata Memorial Centre
Address
Tata Memorial Centre, Department of Medical Oncology, Dr. E.Borges Road, Parel , Mumbai, India
Basavatarakam Indo-American Cancer Hospital and Research Institute
Road no.10, Banjara hills, Hyderabad-500034, Telangana State Hyderabad ANDHRA PRADESH
9866154503 4023542120 mvtkm@yahoo.com
Dr Hemant Malhotra
Birla Cancer Centre, SMS Medical College Hospital
Division of Medical Oncology, J.L.N Marg, Jaipur 302004, Rajasthan, India Jaipur RAJASTHAN
9829062040 1415105589 drmalhotrahemant@gmail.com
Dr Raju Chacko
Christian Medical College
Department of Medical Oncology,Ida Scudder Road, Vellore – 632 004, Tamil Nadu, India Vellore TAMIL NADU
9443250124 4164203200 rchacko@cmcvellore.ac.in
Dr Shona Nag
Jehangir Clinical Development Center Pvt. Ltd.
Department of Medical Oncology Jehangir Hospital, 32 Sassoon Road, Pune - 411 001, Maharashtra Pune MAHARASHTRA
9371072441 912026059319 shona_nag@hotmail.com
Dr Mandar Nadkarni
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute
Medical Research Room, 2nd Floor
Four Bungalows Andheri West
Mumbai- 400053, MAHARASHTRA
India Mumbai MAHARASHTRA
Lake area, Melur road, Madurai 625017, India Madurai TAMIL NADU
9380417299 04522586353 kkrathnam@gmail.com
Dr Dinesh Chandra Doval
Rajiv Gandhi Cancer Institute and Research Centre
Sector-V,Rohini, Delhi 110085 New Delhi DELHI
01147022428 01127051037 dcdoval@gmail.com
Dr Deepak Dabkara
Tata Medical Center
Medical Oncology,Room No 23,
14, Tata Medical Center, MAR(E-W), New Town,Rajarhat, Kolkata-700156, Kolkata WEST BENGAL
8697268292
deepak.dabkara@tmckolkata.com
Dr Sudeep Gupta
Tata Memorial Centre
Tata Memorial Centre, Room No. 1109, 11th Floor, Homi Bhabha Block, Tata Memorial Hospital,Department of Medical Oncology, Dr. E.Borges Road, Parel , Mumbai -400012, India Mumbai MAHARASHTRA
Ethics Committee Jehangir Clinical Development Centre Pvt. Ltd.
Approved
Ethics Committee Silver, Christian Medical College
Approved
Ethics Committee, M. S. Ramaiah Medical College & Hospital
Approved
Institutional Ethics Committee, Basavatarakam Indo-American Cancer Hospital & Research Institute
Approved
Institutional Ethics Committee, Max Super Specialty Hospital (a unit of Balaji Medical & Diagnostic Research Centre)
Approved
Institutional Ethics Committee, Tata Medical Centre, Kolkata
Approved
Institutional Ethics Committee, Tata Medical Centre, Mumbai
Approved
Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre
Approved
Institutional Scientific and Ethics Board, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
The target population for this study is male or female patients with HER2-positive advanced
breast cancer (locally recurrent, unresectable, or metastatic). ,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
NA
NA
Intervention
PERTUZUMAB,
TRASTUZUMAB,
DOCETAXEL
Pertuzumab, trastuzumab, and docetaxel chemotherapy will be administered in line with the PI. Docetaxel treatment will be given at least for 6 treatment cycles; thereafter decision for continuation of docetaxel treatment will be based on investigator’s discretion
Each treatment cycle is 3 weeks (21 days) in duration. The initial dose (Cycle 1, Day 1) of pertuzumab will be 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
The initial dose of trastuzumab will be 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Female
Details
1. Male or female patients age ≥18 years
2. Signed, written informed consent (approved by the relevant Institutional Review Board [IRB]/Ethics Committee[EC]), prior to any study procedure
3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; patients with measurable and/or non-measurable disease are eligible
4. Known and documented HER2-positive (defined as either immunohistochemistry [IHC] 3+ or
in situ hybridization [ISH] positive) as assessed on primary tumor and/or metastatic site if primary tumor not available (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests,a HER2 gene count greater than 4) as determined in a local laboratory that is
experienced/certified in HER2-expression testing using an accurate and validated assay
5. Known and documented LVEF of at least 50%
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
7. A negative serum β-HCG test for women of childbearing potential (premenopausal, or <12
months of amenorrhea post-menopause, and women who have not undergone surgical sterilization [i.e., absence of ovaries and/or uterus]) within 7 days prior to the first dose of
study treatment with the result available prior to first dosing
8. For women of childbearing potential and men with partners of childbearing potential,
agreement to use a highly-effective non-hormonal form of contraception or two effective
forms of non-hormonal contraception by the patient and/or partner. Contraception use must
continue for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. (for women of childbearing potential: agreement to remain abstinent (only if it is in line with
the preferred and usual lifestyle) or use single or combined non-hormonal contraceptive
methods that result in a failure rate of <1% per year during the treatment period and for at
least 7 months after the last dose of study drug)
9. Adequate organ function, as determined by the following laboratory results, within 3 days
prior to study treatment:
· Absolute neutrophil count >1,500 cells/mm3
· Platelet count >100,000 cells/mm3
· Hemoglobin >9 g/dL. (patients may receive transfused red blood cells to obtain this
level)
· Albumin >2.5 g/dL
· Total bilirubin ≤1.5 times the upper limit of normal (ULN), unless the patient has
documented Gilbert’s syndrome
· Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
>2.5 × ULN (>5 × ULN for patients with liver metastases)
· Alkaline phosphatase (ALP) >2.5 × ULN (>5 × ULN in patients with liver metastases or
>10 × ULN for patients with bone metastases)
· Serum creatinine >2.0 mg/dL or 177 mmol/L
· International normalized ratio (INR), activated partial thromboplastin time (aPTT) or
partial thromboplastin time (PTT) <1.5 × ULN (unless on therapeutic anti-coagulation)
ExclusionCriteria
Details
1. Previous systemic non-hormonal anticancer therapy for the metastatic or locally recurrent disease
2. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neo-adjuvant setting
3. Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting
4. History of persistent Grade 2 or higher (NCI-CTCAE, Version 4.03) hematologic toxicity resulting from previous adjuvant or neo-adjuvant therapy
5. Current, known peripheral neuropathy of Grade 3 or greater (NCI-CTCAE, Version 4.03)
6. History of other malignancy within the last 5 years prior to 1st study drug administration (dosing), except for carcinoma in situ of the cervix or basal cell carcinoma
7. Serious uncontrolled concomitant disease that would contraindicate the use of any drug used in this study or that would put the patient at high risk for treatment-related complications
8. Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) or clinically significant (i.e. active and/or requiring medication) cardiovascular disease, including but not limited to cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, CHF of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication, or other cardiovascular problem that is uncontrolled or is currently controlled with medication
9. Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
10. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
11. Major surgical procedure or significant traumatic injury within 14 days prior to 1st study drug administration (dosing) or anticipation of need for major surgery during the course of study treatment
12. Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
13. History of receiving any investigational treatment within 28 days prior to first study drug administration (dosing) and/or concurrent participation in any interventional clinical trial
14. Pregnant or lactating women
15. CNS Metastasis
16. LVEF decline to below 50 percentage
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The primary outcome measures for this study are on safety evaluation
• Incidence and severity of AEs and serious adverse events (SAEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03
• Incidence of congestive heart failure (CHF) and/or significant decline in LVEF
• LVEF over the course of the study
• Laboratory results abnormalities
• Incidence of AEs leading to discontinuation, modification, or interruption of study medication
• Incidence and cause of death due to AEs
Secondary Outcome
Outcome
TimePoints
The secondary outcome measures for this study are on efficacy evaluation
• Overall response rate (assessed by RECISTv1.1)
• Progression-free survival (assessed by RECISTv1.1)
• Overall Survival Patients who were alive at the time of the analysis will be censored at the date of the last follow-up assessment (two years from last patient enrolled in the study)
Target Sample Size
Total Sample Size="52" Sample Size from India="52" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This
is a Phase IV, single-arm, open-label, multicenter study to assess the safety
and efficacy of pertuzumab in combination with trastuzumab and docetaxel for
the treatment of patients with HER2-positive advanced (locally recurrent,
unresectable, or metastatic) breast cancer. Patients must not have received
systemic non-hormonal anticancer therapy for their locally recurrent,
unresectable, or metastatic disease.
The use of the combination
of pertuzumab with trastuzumab may be explained by their complementary mode of
action, while pertuzumab prevents the ligand-activated formation of HER2
heterodimers and homodimers, trastuzumab can block the shedding of HER2
extracellular domain that would result in constitutively activated truncated
receptors. Furthermore, as the two antibodies are not competing for the same
binding epitope on HER2, their combination may lead to a higher antibody load,
resulting in increased tumor-cell killing via ADCC. A total of 52 patients
will be enrolled over duration of approximately 12 months.
Pertuzumab, trastuzumab, and
docetaxel chemotherapy will be administered in line with the PI. Docetaxel
treatment will be given at least for 6 treatment cycles; thereafter decision
for continuation of docetaxel treatment will be based on investigator’s
discretion.Patients will receive study medication till disease progression or
unacceptable toxicity or withdrawal of consent or death, whichever occurs
first.All patients will be followed-up for at least 2 years after the last
patient is enrolled; unless they have been lost to follow up, withdrawn
consent, or died, or the study has been prematurely terminated by the
Sponsor.Tumor assessments will be conducted every 9 weeks from the Day 1 of
first treatment cycle, i.e., every 3 cycles of monoclonal antibody treatment.
Tumor assessments will be conducted during the follow-up period until
progressive disease (PD) has been established, even if treatment has been
discontinued due to unacceptable toxicity