Oropharyngeal CarcinomaPhase 2NCT06984861
A Study of Reduced Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer
A Phase 2 study testing 18F-FMISO PET/CT Scan, Chemoradiation and Questionnaires in people with Oropharyngeal Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oropharyngeal Carcinoma
- What is being tested?
- 18F-FMISO PET/CT Scan, Chemoradiation and Questionnaires
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 7 sitesUnited States
- Study dates
- 13 May 2025to May 2028
- 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
- Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status.
- Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI. Patient must have excisional biopsy or core biopsy done in order to be on protocol.
- Note: Evidence of HPV associated oropharyngeal cancer from either the primary tumor site or from a lymph node. A patient is HPV positive when he or she tests positive having tested positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization.
- Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
- T3-4/N0-2c or any N3 regardless of Tstage (AJCC 7th Edition) HPV+ OPC* or HPV associated squamous cell carcinoma with nodal metastasis (es) but unknown primary sites without evidence of distant metastasis based on FDG PET/CT.
- CT Neck with contrast or MRI of the neck with and without contrast Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.
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- ECOG Performance Status of 0-2 or KPS ≥ 70
- Age ≥ 18
- Adequate hematologic function within 30 days prior to registration, defined as follows:
- White Blood Count (WBC) ≥ 2 K/mcL
- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm^3
- Platelets ≥ 100,000 cells/mm^3
- Hemoglobin ≥ 8.0 g/dl
- Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
- Adequate renal function within 30 days prior to registration, defined as follows:
- Serum creatinine ≤ 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male) Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel
- Adequate hepatic function within 30 days prior to registration, defined as follows:
- Bilirubin ≤ 2 mg/dl
- AST or ALT ≤ 3 x the upper limit of normal Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
- One cycle of induction chemo therapy is allowed prior to registration based on clinical needs.
- The subject must provide study-specific informed consent prior to study entry Subject able to undergo MRI scans except for major medical contraindications like presence of a pacemaker or approved by the PI or the CO-PI that the subject does not need to undergo MRI scans
Who cannot join
- Subjects with prior head and neck radiation therapy
- Subjects with simultaneous primary cancers outside of the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
- Note: Exceptions can be made for patients with simultaneous primaries outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- Severe, active co-morbidity defined as follows (exceptions can be made if approved by the PI and/or co-PI)
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- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- Transmural myocardial infarction within the last 6 months
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
- Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Nadeem Riaz, MD contact
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Suffolk- Commack (Limited Protocol Activities)
Commack, New York, 11725
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Nancy Lee, MD, 212-639-3341
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Nancy Lee, MD, 212-639-3341
About this study
Official title: Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Advanced Stage Human Papilloma Virus Associated Oropharyngeal Carcinoma
The researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the standard doses of radiation therapy in combination with standard-of-care chemotherapy. The chemotherapy drugs used in combination with radiation therapy in this study include cisplatin, carboplatin, and 5-fluorouracil (5-FU).
- Conditions
- Oropharyngeal Carcinoma
- Being tested
- 18F-FMISO PET/CT Scan, Chemoradiation, Questionnaires
- Keywords
- Human Papilloma Virus Associated, Chemoradiation, T3-4/N0-2c or any N3, 25-040
- Medical subject headings
- Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18F-FMISO PET/CT ScanDiagnostic test
The 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. Subjects will undergo 18F-FMISO scan (only 1 injection) occurs at 8-10 treatment days* into chemoradiation. Each patient will have a baseline staging FDG PET scan which is used to localize the tumor at the primary site and all suspicious cervical neck nodes (> 1 cm in short axis diameter with focal abnormal increased FDG avidity). These lesions are then assessed on the respective 18F-FMISO PET/CT.
ChemoradiationCombination product
Patients will start with induction chemotherapy of carboplatin, paclitaxel and cetuximab for 6 weeks and when downstaged to T1-2 and < N3, the patient is eligible to receive concurrent chemoradiation per protocol. All subjects will undergo radiation treatments (IMRT and/or proton therapy). A total radiation therapy of 30Gy will be delivered to the oropharynx and neck at 2Gy per fraction per day over 15 days for patients who exhibited no evidence of hypoxia on the intra-treatment 18F-FMISO PET/CT. Concurrent chemotherapy (2 cycles) will be given. After completion of chemotherapy and radiation therapy, a 4 month (+/-4 weeks)
QuestionnairesOther
EQ-5D-5L, MDADI-HN, COST-FACIT
| Study group | Role | What they receive |
|---|---|---|
| Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer | Experimental | Subjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and <N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline. Receives: Diagnostic Test: 18F-FMISO PET/CT Scan; Combination Product: Chemoradiation; Other: Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
Locoregional control
Researchers will test the null hypothesis H0: P=78% vs the alternative hypothesis H1:P=91%, where P represents the 2-year locoregional control (LRC). We will use the Kaplan-Meier method to estimate the LRC rate at 2 years and construct a 0.975 1-sided confidence interval in order to achieve a test size alpha = 0.05 (this is based on a finite-sample correction using 100,000 simulations).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2025
- Study start13 May 2025
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oropharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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
- This non-randomized phase II study.
- Masking
- None (open label)
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nancy Lee, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06984861
- Sponsor's protocol ID
- 25-040
- Status last verified
- May 2026
- First submitted
- 14 May 2025
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Advanced Stage Human Papilloma Virus Associated Oropharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT06984861
- Acronym / sponsor ID
- 25-040
- Conditions
- Oropharyngeal Carcinoma
- Keywords
- Human Papilloma Virus Associated, Chemoradiation, T3-4/N0-2c or any N3, 25-040
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 13 May 2025 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 22 May 2025 (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 researchers are doing this study is to find out if lower doses (given in fewer treatments over a shorter period of time) of radiation therapy in combination with standard-of-care chemotherapy is an effective treatment for people with Human Papilloma Virus (HPV)-positive throat cancer and works as well as the standard doses of radiation therapy in combination with standard-of-care chemotherapy. The chemotherapy drugs used in combination with radiation therapy in this study include cisplatin, carboplatin, and 5-fluorouracil (5-FU).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This non-randomized phase II study.
| Arm | Type | Receives |
|---|---|---|
| Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer | Experimental | Diagnostic Test: 18F-FMISO PET/CT Scan, Combination Product: Chemoradiation, Other: QuestionnairesSubjects will first undergo 6 weeks of standard induction chemotherapy and if downstaged to T1-2 and <N3 and also have no evidence of hypoxia will undergo a major de-escalated radiation therapy to 30Gy concurrent with standard chemotherapy. Hypoxia status is determined by the absence of hypoxia uptake on Fluorine-18-Labeled Fluoro-Misonidazole (18F-FMISO) PET/CT imaging (8-10 treatment days after start of chemoradiation), which has an FDA approved IND for use in humans . If the 18F-FMISO PET is negative for hypoxia, the patient will receive 30Gy concurrent with 2 cycles of chemotherapy. If the 18F-FMISO PET is positive for hypoxia, the patient will receive standard of care 70Gy concurrent with 3 cycles of chemotherapy. An optional 18F-FMISO scan will also be offered at baseline. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status.
- Note: Evidence of HPV associated oropharyngeal cancer from either the primary tumor site or from a lymph node. A patient is HPV positive when he or she tests positive having tested positive for both p16 expression (70% nuclear and cytoplasm expression; Ventana Medical Systems) and mRNA HPV in situ hybridization.
- Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
- T3-4/N0-2c or any N3 regardless of Tstage (AJCC 7th Edition) HPV+ OPC* or HPV associated squamous cell carcinoma with nodal metastasis (es) but unknown primary sites without evidence of distant metastasis based on FDG PET/CT.
- CT Neck with contrast or MRI of the neck with and without contrast Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.
Key exclusion criteria (11 listed)
- Subjects with prior head and neck radiation therapy
- Subjects with simultaneous primary cancers outside of the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
- Note: Exceptions can be made for patients with simultaneous primaries outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
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 |
|---|---|---|
| 18F-FMISO PET/CT ScanThe 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. Subjects will undergo 18F-FMISO scan (only 1 injection) occurs at 8-10 treatment days* into chemoradiation. Each patient will have a baseline staging FDG PET scan which is used to localize the tumor at the primary site and all suspicious cervical neck nodes (> 1 cm in short axis diameter with focal abnormal increased FDG avidity). These lesions are then assessed on the respective 18F-FMISO PET/CT. | Diagnostic test | Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer |
| ChemoradiationPatients will start with induction chemotherapy of carboplatin, paclitaxel and cetuximab for 6 weeks and when downstaged to T1-2 and < N3, the patient is eligible to receive concurrent chemoradiation per protocol. All subjects will undergo radiation treatments (IMRT and/or proton therapy). A total radiation therapy of 30Gy will be delivered to the oropharynx and neck at 2Gy per fraction per day over 15 days for patients who exhibited no evidence of hypoxia on the intra-treatment 18F-FMISO PET/CT. Concurrent chemotherapy (2 cycles) will be given. After completion of chemotherapy and radiation therapy, a 4 month (+/-4 weeks) | Combination product | Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer |
| QuestionnairesEQ-5D-5L, MDADI-HN, COST-FACIT | Other | Radiation Therapy With Chemotherapy in People With HPV-Positive Throat Cancer |
Primary outcome
Locoregional control
Time frame: 2 years
Researchers will test the null hypothesis H0: P=78% vs the alternative hypothesis H1:P=91%, where P represents the 2-year locoregional control (LRC). We will use the Kaplan-Meier method to estimate the LRC rate at 2 years and construct a 0.975 1-sided confidence interval in order to achieve a test size alpha = 0.05 (this is based on a finite-sample correction using 100,000 simulations).
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 11 May 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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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.
Nadeem Riaz, MD contact
Nancy Lee, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 18F-FMISO PET/CT Scan, Chemoradiation and Questionnaires in people with Oropharyngeal Carcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
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 21 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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 Nancy Lee, MD (212-639-3341, leen2@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Locoregional control (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 May 2026.