CTRI/2017/03/008034 [Registered on: 07/03/2017] Trial Registered Prospectively
Last Modified On:
28/11/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Study of Palbociclib taken together with letrozole for treatment of Post-Menopausal Women with Advanced Breast Cancer
Scientific Title of Study
A Study of Palbociclib in Combination With Letrozole as Treatment of Post-Menopausal Women With Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer for Whom Letrozole Therapy is Deemed Appropriate
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
A5481037 Amendment Number 3, Dated 31-May-2016
Protocol Number
NCT02679755
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
All India Institute of Medical Sciences - Dr. B.R.A Institute Rotary Cancer Hospital
Dr. B.R.A Institute Rotary Cancer Hospital, Department of Radiation Oncology, All India Institute of Medical Sciences,
Ansari Nagar, New Delhi – 110029, India
New Delhi DELHI
Ethics Committee of Manipal Hospitals - Dr. Rauthan Amit Deenabandhu
Submittted/Under Review
GCRI/ GCS Ethics Committee - Dr. Harsha P Panchal
Approved
HCG- Ethics Committee - Dr. Viveka B. K
Approved
Institutional Ethics Committee AIIMS - Dr. Haresh KP
Submittted/Under Review
Institutional Ethics Committee Deenanath Mangeshkar Hospital & Research Centre - Dr. Sambhus Mahesh Bindumadav
Submittted/Under Review
Institutional Ethics Committee, Tata Memorial Hospital - Dr. Badwe Rajendra Achyut
Approved
Institutional Ethics Committee- Clinical Studies, Apollo Hospitals Enterprise Limited - Dr. Raja Madras Ananthanarayanan
Approved
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre - Dr. Dinesh Chandra Doval
Approved
Manipal University Ethics Committee, Manipal - Dr. Donald J Fernandes
Approved
Meditrina Institutional Ethics Committee - Dr. Anand Bhaskarrao Pathak
Approved
Sahyadri Hospitals Ltd Ethics Committee - Dr. Vinod Tatyasaheb Gore
Approved
Shatabdi Hospital Ethics Committee - Dr. Shailesh Arjun Bondarde
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Hormone receptor-positive, HER2-negative Advanced Breast Cancer for whom Letrozole therapy is deemed appropriate in first line in advanced/metastatic setting,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
NIL
NIL
Intervention
Palbociclib 75 mg, 100 mg, or 125 mg and Letrozole 2.5 mg
Palbociclib capsules containing 75 mg, 100 mg, or 125 mg equivalents of palbociclib free base
Letrozole will be administered orally at 2.5 mg once daily
Duration 18 Months
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Female
Details
Patient eligibility should be reviewed and documented by an appropriate member of the investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Women of ≥18 years of age with proven diagnosis of advanced adenocarcinoma of the breast (locoregionally recurrent or metastatic disease).
2. Post-menopausal status defined as per local practice
3. ER(+) and/or PgR(+) tumor based on local laboratory results (test as per local practice)
4. HER2(-) breast cancer based on local laboratory results (test as per local practice or local guidelines)
5. Patients must be appropriate candidates for letrozole therapy. (in the first-line advanced/metastatic disease setting).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
7. Adequate bone marrow function:
• Absolute Neutrophil Count (ANC) ≥1,500/mm3 (1.5 x 109 /L);
• Platelets ≥100,000/mm3 (100 x 109 /L);
• Hemoglobin ≥9 g/dL (90 g/L).
8. Adequate liver function:
• Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) ≤3 x Upper Limit of Normal (ULN) (≤5.0 x ULN if liver metastases present);
• Alkaline phosphatase ≤2.5 x ULN (≤5.0 x ULN if bone or liver metastases present);
• Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease).
9. Adequate renal function:
• Serum creatinine ≤1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min
10. Resolution of all acute toxic effects of prior therapy, including radiotherapy to grade ≤1 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures.
11. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
12. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
ExclusionCriteria
Details
Patients presenting with any of the following will not be included in the study:
1. Known hypersensitivity to letrozole, or any of its excipients, or to any palbociclib excipients.
2. Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4 isoenzymes within 7 days prior to study entry
3. Prior treatment with any CDK inhibitor.
4. Previous participation in a palbociclib trial.
5. Participation in other studies involving investigational drug(s) (Phases 1-4) within 2 weeks before the current study begins and/or during study participation.
6. QTc >480 msec (based on the mean value from triplicate electrocardiograms [ECGs]; see Appendix 2 of Protocol Amendment 3 dated 31 May 2016 for suggested QTc calculation); history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
7. High cardiovascular risk, including, but not limited to recent myocardial infarction, severe/unstable angina and severe cardiac dysrhythmias in the past 6 months of enrollment.
8. Diagnosis of any second malignancy within the last 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
9. Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, as per Investigator’s judgment, brain metastases are permitted.
10. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
11. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees directly involved in the conduct of the study.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Percentage of patients with treatment-emergent adverse events (AEs) or serious adverse events (SAEs)
Baseline up to 28 days after last dose of study treatment
Secondary Outcome
Outcome
TimePoints
Objective Response
Baseline and per routine clinical practice to time of last dose of study treatment, up to 24 months
Change from Baseline in Dimension Health State EuroQol (EQ-5D) Score
Baseline, Day 1 of each cycle up to 3 years
Target Sample Size
Total Sample Size="300" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "252" Final Enrollment numbers achieved (India)="100"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is an open-label, single arm, multinational, multicenter clinical trial. Post-menopausal women with HR-Positive and HER2-Negative Advanced Breast Cancer will be enrolled. Patients will have histologically or cytologically proven diagnosis of adenocarcinoma of the breast (locoregionally recurrent or metastatic disease) and will be candidates to receive letrozole as their best therapeutic option.
Patients will continue to receive treatment with palbociclib and letrozole until disease progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first. Patients who permanently discontinue palbociclib or letrozole for any reason will be off study.
Approximately 100 patients will be enrolled in this study from India.