Study of Pembrolizumab in Metastatic HER2-negative Breast Cancer Patients With APOBEC3B Mutation
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|ClinicalTrials.gov Identifier: NCT03989089|
Recruitment Status : Recruiting
First Posted : June 18, 2019
Last Update Posted : July 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|HER2-Negative Breast Cancer||Drug: Pembrolizumab||Phase 2|
This is an open label investigator initiated Phase II study of single agent pembrolizumab (Keytruda®) in metastatic HER2-receptive negative breast cancer patients with germline deletion in the cytosine deaminase (APOBEC3B) gene. Approximately 44 subjects will be enrolled in this study to examine the efficacy of pembrolizumab when given 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (2 years). ER+ patients need to have failed at least one line of prior hormonal treatment. All patients need to have failed at least one line, but no more than 3 lines, of prior chemotherapy in the metastatic setting.
Disease status will be followed by imaging studies at 9 weekly interval (± 7 days) during the first year, independent of any treatment delays, and every 12 weeks (±7 days) after the first year, until disease progression, start of non-study treatment, withdrawal of consent to study participation, death or end of the study. RECIST 1.1 will be used as the primary efficacy endpoint of response rate. Safety will be monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Study treatment will continue until any of the following occurs:
- Disease progression, as defined by Response Evaluation Criteria in Solid Tumour (RECIST version 1.1) (when progressive disease [PD] is confirmed, subject may be further followed up using consensus guideline of modified RECIST 1.1 [iRECIST] criteria);
- Unacceptable toxicity;
- Intercurrent illness that necessitates discontinuation of study treatment;
- Investigator's decision to withdraw the subject,
- Non-compliance with study treatment or procedure requirements;
- Withdrawal of consent to treatment;
- End of the study;
- Other administrative reasons requiring cessation of study treatment.
This study will be conducted in conformance with Good Clinical Practices.
Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each procedure are provided in Section 7.0 - Trial Procedures.
Subject will be given a pre-screening inform consent form to participate in the genetic testing to determine their APOBEC3B germline mutation status.
Subject with confirmed APOBEC3B germline mutation will be given another inform consent form to participate in the main study.
The primary objective of the trial is to determine the efficacy of pembrolizumab in metastatic HER2-negative breast cancer subjects with APOBEC3B germline deletion polymorphism. Secondary objectives include progression-free survival (PFS), overall survival (OS) and response duration in this subject populations. The relationships of the germline variation, the associated molecular signatures, as well as other potential prognostic biomarkers with the study treatment will be explored as the exploratory objectives.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single group assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II, Single Arm, Open Label, Simon Two-Stage Study of Pembrolizumab in Metastatic HER2-negative Breast Cancer Patients: Evaluation of Impact of Germline Variants in APOBEC3B|
|Actual Study Start Date :||July 3, 2020|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||December 1, 2023|
Experimental: Pembrolizumab single agent
Pembrolizumab 200 mg will be given intravenously every 3 weeks , on Day 1 on each 3 week cycle. Pembrolizumab can be given up to 35 adminstration (2 years).
The planned dose of pembrolizumab for this study is 200 mg every 3 weeks (Q3W). Based on the totality of data generated in the Keytruda® development program, 200 mg Q3W is the appropriate dose of pembrolizumab for adults across all indications and regardless of tumour type.
All participants who off study treatment with stable disease (SD) or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping study treatment from the initial treatment phase. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the participant met certain criteria as stated in the protocol.
Other Name: Keytruda
- Overall response rate (ORR) [ Time Frame: Up to 4 years ]To determine the overall response rate (ORR) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms using RECIST 1.1.
- Progression free survival (PFS) [ Time Frame: Up to 4 years ]To estimate the progression free survival (PFS) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms.
- Overall survival [ Time Frame: Up to 4 years ]To estimate overall survival (OS) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms.
- Disease control rate [ Time Frame: Up to 4 years ]To estimate the disease control rate (DCR) i.e. complete response (CR), partial response (PR) or stable disease (SD) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphism.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03989089
|Contact: Gwo Fuang Ho, FRCR||+603-79492120 ext email@example.com|
|Contact: Yok Yong Toh||+603-79492120 ext firstname.lastname@example.org|
|University Malaya Medical Centre||Recruiting|
|Kuala Lumpur, Wilayah Persekutuan, Malaysia, 59100|
|Contact: Yok Yong Toh, BA +60379492120 email@example.com|
|Principal Investigator: Gwo Fuang Ho, FRCR|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119228|
|Contact: Priscilla Soh|
|Principal Investigator: Soo Chin Lee|
|Principal Investigator:||Gwo Fuang Y Ho, FRCR||University of Malaya|