Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia
Introduction Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment o...
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BMJ Publishing Group
2024-12-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/14/12/e076898.full |
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| author | Gwo Fuang Ho Soo Hwang Teo Abqariyah Yahya Sok Ching Cheong Kue Peng Lim Bawani Selvam Ibtisam Muhamad Nor Chih Kiang Tan Yoke Fui Wong Annie Wai Yeeng Chai Wan Zamaniah Wan Ishak |
| author_facet | Gwo Fuang Ho Soo Hwang Teo Abqariyah Yahya Sok Ching Cheong Kue Peng Lim Bawani Selvam Ibtisam Muhamad Nor Chih Kiang Tan Yoke Fui Wong Annie Wai Yeeng Chai Wan Zamaniah Wan Ishak |
| author_sort | Gwo Fuang Ho |
| collection | DOAJ |
| description | Introduction Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.Methods and analysis This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.Ethics and dissemination The study was approved by the ethics committee of the University Malaya Medical Centre (202213–10884). Findings will be disseminated through conference presentations and peer review publications.Trial registration number ClinicalTrials.gov (www.clinicaltrial.gov); NCT05286619. |
| format | Article |
| id | doaj-art-9688642184db4aebbdaab1bac0e5a016 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
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| spelling | doaj-art-9688642184db4aebbdaab1bac0e5a0162025-08-20T02:36:28ZengBMJ Publishing GroupBMJ Open2044-60552024-12-01141210.1136/bmjopen-2023-076898Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in MalaysiaGwo Fuang Ho0Soo Hwang Teo1Abqariyah Yahya2Sok Ching Cheong3Kue Peng Lim4Bawani Selvam5Ibtisam Muhamad Nor6Chih Kiang Tan7Yoke Fui Wong8Annie Wai Yeeng Chai9Wan Zamaniah Wan Ishak109 Clinical Oncology, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia1 Cancer Research Malaysia, Subang Jaya, Selangor, MalaysiaInstitute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia2 Department of Oral & Maxillofacial Clinical Sciences, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, Wilayah Persekutuan, Malaysia1Cancer Research Malaysia, Subang Jaya, Malaysia1 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia4 Department of Radiotherapy & Oncology, General Hospital, Kuala Lumpur, Malaysia5 Oncology and Nuclear Medicine Department, Thomson Hospital Kota Damansara, Petaling Jaya, Selangor, Malaysia6 Department of Radiotherapy & Oncology, National Cancer Institute, Putrajaya, Malaysia1 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia3 Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Wilayah Persekutuan, MalaysiaIntroduction Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.Methods and analysis This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.Ethics and dissemination The study was approved by the ethics committee of the University Malaya Medical Centre (202213–10884). Findings will be disseminated through conference presentations and peer review publications.Trial registration number ClinicalTrials.gov (www.clinicaltrial.gov); NCT05286619.https://bmjopen.bmj.com/content/14/12/e076898.full |
| spellingShingle | Gwo Fuang Ho Soo Hwang Teo Abqariyah Yahya Sok Ching Cheong Kue Peng Lim Bawani Selvam Ibtisam Muhamad Nor Chih Kiang Tan Yoke Fui Wong Annie Wai Yeeng Chai Wan Zamaniah Wan Ishak Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia BMJ Open |
| title | Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia |
| title_full | Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia |
| title_fullStr | Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia |
| title_full_unstemmed | Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia |
| title_short | Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia |
| title_sort | pembrolizumab mk 3475 plus platinum and gemcitabine as first line treatment of recurrent metastatic head and neck squamous cell carcinoma piper a phase 2 multicentre single arm protocol study in malaysia |
| url | https://bmjopen.bmj.com/content/14/12/e076898.full |
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