Betel-nut-associated Oral CarcinomaPhase 2NCT07733466
Open-Label Neoadjuvant Pembrolizumab Plus Cetuximab in Betel Nut-Associated Locally Advanced Oral Cavity Squamous Cell Carcinoma
A Phase 2 study testing Pembrolizumab and cetuximab in people with Betel-nut-associated Oral Carcinoma, run by Peter Brett, MD at 1 site in Northern Mariana Islands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Betel-nut-associated Oral Carcinoma
- What is being tested?
- Pembrolizumab and cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNorthern Mariana Islands
- Study dates
- 15 Aug 2026to Jun 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Northern Mariana Islands1 site
Northern Marianas Oncology Center | Commonwealth Healthcare Corporation
Saipan, 96950
Angela Figueroa, MSN, RN, (670) 234-8951 ext. Option 4, angela.figueroa@chcc.health
Beth Davis, (707)388-3852, marybethdavis5544@outlook.com
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Betel-nut-associated Oral Carcinoma
- Being tested
- Pembrolizumab and cetuximab
- Keywords
- cetuximab, pembrolizumab, immunotherapy, betel-nut
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab and cetuximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant pembrolizumab and cetuximab | Other | neoadjuvant treatment Receives: Drug: Pembrolizumab and cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
1.Overall Response Rate to neoadjuvant immunotherapy in patients with treatment naive Stage IIII-IV betal-nut-associated oral cavity carcinoma
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
Measured: Baseline through 84 weeks
Secondary outcomes (1)
1. To evaluate median and 3-year disease-free survival (DFS) following treatment initiation
CT scan results meaured by RECIST 1.1
Measured: Baseline to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2026
- Study start15 Aug 2026 (estimated)
- Primary completionJul 2030 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Betel-nut-associated Oral CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- neoadjuvant
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter Brett, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Peter Brett, MD, Commonwealth Healthcare Corporation
- Investigators
- Peter Brett, MD, Study director, CHCC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07733466
- Sponsor's protocol ID
- NB600390
- Status last verified
- Jul 2026
- First submitted
- 27 Jun 2026
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patient data
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.
PubMed 2702835Yang 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.
PubMed 32492239Narayanan 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.
PubMed 31351740Burtness 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.
PubMed 31679945Rumgay 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.
PubMed 39393386Sacco 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.
PubMed 33989559Yao 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.
PubMed 39138647
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07733466
- Acronym / sponsor ID
- NB600390
- Conditions
- Betel-nut-associated Oral Carcinoma
- Keywords
- cetuximab, pembrolizumab, immunotherapy, betel-nut
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peter Brett, MDUniversity, hospital or other
- Study start
- 15 Aug 2026 (estimated)
- Primary completion
- Jul 2030 (estimated)
- Study completion
- Jun 2031 (estimated)
- First posted
- 29 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- neoadjuvant
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant pembrolizumab and cetuximab | Other | Drug: Pembrolizumab and cetuximabneoadjuvant treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab and cetuximabneoadjuvant 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. | Drug | Neoadjuvant pembrolizumab and cetuximab |
Primary outcome
1.Overall Response Rate to neoadjuvant immunotherapy in patients with treatment naive Stage IIII-IV betal-nut-associated oral cavity carcinoma
Time frame: 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
1 secondary outcome
1. To evaluate median and 3-year disease-free survival (DFS) following treatment initiation
Time frame: Baseline to 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Background: PubMed 2702835Simon 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.
- Background: PubMed 32492239Yang 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.
- Background: PubMed 31351740Narayanan 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.
- Background: PubMed 31679945Burtness 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.
- Background: PubMed 39393386Rumgay 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.
- Background: PubMed 33989559Sacco 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.
- Background: PubMed 39138647Yao 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.
- Individual participant dataSharing planned: Yes. Patient data
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Brett, MD study director
CHCC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and cetuximab in people with Betel-nut-associated Oral Carcinoma, run by Peter Brett, MD at 1 site in Northern Mariana Islands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Northern Mariana Islands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Peter Brett, MD ((670) 234-8950, peter.brett@chcc.health), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1.Overall Response Rate to neoadjuvant immunotherapy in patients with treatment naive Stage IIII-IV betal-nut-associated oral cavity carcinoma (time frame: Baseline through 84 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07733466, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.