Neoadjuvant Pembrolizumab Plus Cetuximab in Betel Nut-Associated Locally Advanced Oral Cavity Squamous Cell Carcinoma in the Commonwealth of the Northern Mariana Islands: A Prospective, Open Label, Single Arm, Single Center, Non-randomized, Phase 2 Trial
| Registry | NCT07733466 |
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| Status | Not yet recruiting |
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| Phase | Phase 2 |
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| Study type | Interventional; na, single group, masking: none, treatment |
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| Enrollment | 20 (Estimated) |
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| Sponsor | Peter Brett, MD (Other) |
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| Conditions | Betel-nut-associated Oral Carcinoma |
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| Interventions | Pembrolizumab and cetuximab (Drug) |
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| Dates | start 2026-08-15 (estimated), primary completion 2030-07-01 (estimated), completion 2031-06-01 (estimated), first posted 2026-07-29, last updated 2026-08-10 |
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| Locations | 1 site in Northern Mariana Islands |
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Related Papers Related Patents Related Grants Related Experts
All trials for Betel-nut-associated Oral Carcinoma All trials of Pembrolizumab and cetuximab
-Summary
The goal of this clinical trial is to learn the overall response rate of giving immunothrapy before surgery in treatment-naive, advanced stage patients with Betal-nut-associated oral cavity cancer.
The outcomes to be measured by CT scan are overall response rate of either partial or complete response.
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+Detailed description
Neoajuvant treatment with IV pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph SQ will be given every 6 weeks in 2, 6 week cycles, with IV cetuximab to be given every 2 weeks in 2, 6 week cycles. Disease will be measured by CT scan pre-treatment and at 6 and12 weeks. Following neoadjuvant treatment, patients will attend the University of Southern California 2 to 6 weeks later for SOC chemotherapy and radiation therapy if deemed necessary.
+Arms and interventions
| Arm | Type | Interventions | Description |
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| Neoadjuvant pembrolizumab and cetuximab | Other | Drug: Pembrolizumab and cetuximab | neoadjuvant treatment |
- Pembrolizumab and cetuximab (Drug): neoadjuvant immunotherapy using: 400 mg IV pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph 760 mg SQ given 2 times with cetuximab 500 mg/m2 IV every 2 weeks over a 12 week period.
+Outcome measures
Primary outcomes
- 1.Overall Response Rate to neoadjuvant immunotherapy in patients with treatment naive Stage IIII-IV betal-nut-associated oral cavity carcinoma [Baseline through 84 weeks]: Assess ORR by CT scan using RECIST 1.1 in patients with treatment naive, advanced Stage III-IV Betel-Nut Associated oral cavity squamous cell carcinoma
Secondary outcomes
- 1. To evaluate median and 3-year disease-free survival (DFS) following treatment initiation [Baseline to 36 months]: CT scan results meaured by RECIST 1.1
Other outcomes
- To evaluate overall survival [Baseline to 36 months]: Overall survival
- To evaluate recurrence-free survival [Baseline to 36 months]: CT scan measured by RECIST 1.1
- To characterize safety and tolerability of this neoadjuvant treatment regimen [Baseline to 84 weeks]: Measured by rate of treatment-related adverse events per NCI-CTCAE version 6.0 and immune related events
- To determine the rate of downstaging [From baseline through 42 weeks]: assessed between pre-treatment clinical stage and post-treatment pathological stage, and rate of positive surgical margins
- To assess rate of surgical complications [At surgery]: Surgical complications found by surgeon
- Rate of adjuvant chemo and radiation therapy [Post-surgery at 14 to 18 weeks]: Rate of need for chemo and radiation following surgery
- To assess need for tracheotomy [3 months following surgery]: Determine rate of tracheotomy post-surgery
- To determine median time between neoadjuvant treatment and surgery [Between 12 weeks and 18 weeks from baseline]: TIme between neoadjuvant treatment cessation and surgical resection
- To determine the rate of surgical resectability [At 14 to 18 weeks following baseline]: Achievement of negative pathologic margins at surgery
- Assess need for gastrostomy [At 3 months post-surgery]: Following surgery
- Assess oral incompetence [3 months following surgery]: Assess need for gastrostomy tube
- Subjectively assess trismus [At 6 months post-surgery]: Physician assessment of trismus post-treatment-surgery
+Eligibility
Sex: All, ages: 18 Years to any
Inclusion Criteria:
* Documented history of betel-nut chewing
* confirmed oral cavity squamous cell carcinoma
* measurable disease via RECIST 1.1
* Clinical stage III/IV per AJCC 8th edition
* treatment-naive
* ECOG 0-3
Exclusion Criteria:
* Distant metastatic disease
* prior treatment for current cancer
* active immune disease or other condition requiring immunosuppression or chronic corticosteroid use
* active pneumonitis
* known hypersensitivity to pembrolizumab or cetuximab
* pregnant or breast-feeding
* women of childbearing potential without willingness to use contraception during the trial
+Locations (1)
| Facility | City | Country | Status |
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| Northern Marianas Oncology Center | Commonwealth Healthcare Corporation | Saipan | Northern Mariana Islands | |
+Publications
- Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9. PMID 2702835
- Yang J, Wang ZY, Huang L, Yu TL, Wan SQ, Song J, Zhang BL, Hu M. Do betel quid and areca nut chewing deteriorate prognosis of oral cancer? A systematic review, meta-analysis, and research agenda. Oral Dis. 2021 Sep;27(6):1366-1375. doi: 10.1111/odi.13456. Epub 2020 Jun 26. PMID 32492239
- Narayanan AM, Finegersh A, Chang MP, Ogo J, Orosco RK, Moss WJ. The profound oral cavity cancer burden in the United States Commonwealth of the Northern Mariana Islands: A global health opportunity. Am J Otolaryngol. 2019 Nov-Dec;40(6):102267. doi: 10.1016/j.amjoto.2019.07.011. Epub 2019 Jul 19. PMID 31351740
- Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1. PMID 31679945
- Rumgay H, Nethan ST, Shah R, Vignat J, Ayo-Yusuf O, Chaturvedi P, Guerra ENS, Gupta PC, Gupta R, Liu S, Magnusson C, Parascandola M, Paulino YC, Rezaei N, Siddiqi K, Warnakulasuriya S, Lauby-Secretan B, Soerjomataram I. Global burden of oral cancer in 2022 attributable to smokeless tobacco and areca nut consumption: a population attributable fraction analysis. Lancet Oncol. 2024 Nov;25(11):1413-1423. doi: 10.1016/S1470-2045(24)00458-3. Epub 2024 Oct 8. PMID 39393386
- Sacco AG, Chen R, Worden FP, Wong DJL, Adkins D, Swiecicki P, Chai-Ho W, Oppelt P, Ghosh D, Bykowski J, Molinolo A, Pittman E, Estrada MV, Gold K, Daniels G, Lippman SM, Natsuhara A, Messer K, Cohen EEW. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):883-892. doi: 10.1016/S1470-2045(21)00136-4. Epub 2021 May 11. PMID 33989559
- Yao Z, Wang J, Jiang Y, Zhang Y, Liu J, Dai L, Shen S, Zhou X, Liu Q, Zheng L, Qian M, Li J. Pembrolizumab plus cetuximab with neoadjuvant chemotherapy for head and neck squamous cell carcinoma. Head Neck. 2025 Jan;47(1):289-299. doi: 10.1002/hed.27915. Epub 2024 Aug 13. PMID 39138647
+Investigators