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HPV-Associated Oropharyngeal Squamous Cell CarcinomaPhase 2NCT03323463

Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma

A Phase 2 study testing F-FMISO PET/CT Scan, 30 Gy over 3 weeks and Cisplatin in people with HPV-Associated Oropharyngeal Squamous Cell Carcinoma and Squamous Cell Carcinoma of the Neck, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to demonstrate that participants with HPV positive and hypoxia negative T1-2, N1-2c (AJCC, 7th ed.) oropharyngeal squamous cell carcinoma receiving a major de-escalated radiation therapy with 2 cycles of standard chemotherapy is not inferior to comparable subjects treated with the current… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
F-FMISO PET/CT Scan, 30 Gy over 3 weeks and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
316 participants
Where
10 sitesUnited States
Study dates
16 Oct 2017to 31 Oct 2026
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

  • Cohort A: Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from 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) and consent from the PI or co-PIs
  • Cohort B: Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls). Surgical removal of primary site is no longer required.
  • Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) and consent from the PI or co-PIs
  • Subjects must have clinically or radiographically evident measurable disease at nodal stations.
  • Clinical stage T1-2, N1-2c without evidence of distant metastasis based on FDG PET/CT.
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  • Patients who have squamous cell carcinoma of the neck of unknown primary, and thus, are T0, are allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI
  • CT 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.
  • ECOG Performance Status of 0-2 or Karnopsky Performance Status >/= 50
  • 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/mm3
  • Platelets ≥ 100,000 cells/mm3
  • 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)
  • 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
  • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
  • The subject must provide study-specific informed consent prior to study entry

Who cannot join

  • Subjects with prior head and neck radiation therapy
  • Subjects with simultaneous primary cancers outside of the oropharynx
  • 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
  • No particle therapy such as but not limited to proton therapy is allowed in Cohort A. For Cohort B, this exclusion is removed.
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  • Severe, active co-morbidity defined as follows:
  • 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

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Hartford Healthcare (Data Collection)

    Hartford, Connecticut, 06102

  • Baptist Alliance MCI (Data Collection Only)

    Miami, Florida, 33143

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

  • Memorial Sloan Kettering Rockville Centre

    Rockville Centre, New York, 11570

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: A Prospective Single Arm Non-inferiority Trial of Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma (Major De-escalation to 30Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma)

The purpose of this study is to demonstrate that participants with HPV positive and hypoxia negative T1-2, N1-2c (AJCC, 7th ed.) oropharyngeal squamous cell carcinoma receiving a major de-escalated radiation therapy with 2 cycles of standard chemotherapy is not inferior to comparable subjects treated with the current standard chemoradiation.

Accrual for Cohort A has been completed.

Cohort B is active and continues to enroll participants where surgery is optional and proton is allowed.

Read the detailed description

This non-randomized non-inferiority study will enroll HPV associated oropharyngeal carcinoma subjects. Subjects who also have no evidence of hypoxia will undergo a major de-escalated radiation therapy concurrent with standard chemotherapy. Hypoxia status will be determined by 1 BF-FMISO PET /CT imaging. If this baseline scan shows no evidence of hypoxia, the subject will receive 30Gy concurrent with 2 cycles of chemotherapy. If this baseline scan shows evidence of hypoxia, a repeat 1 BF-FMISO scan will be done 5-10 treatment days after start of radiation therapy. If the repeat 1 BF-FMISO scan PET /CT demonstrates no evidence of hypoxia, the subject will receive 30Gy concurrent with 2 cycles of chemotherapy. If the repeat 1 BF-FMISO scan PET /CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy. At 4 (+/- 4 weeks) months after chemoradiation, a neck dissection will be done unless the subjects FDG PET /CT scan at that time shows no evidence of disease of which the subject can be observed as per current standard of care.

Being tested
F-FMISO PET/CT Scan, 30 Gy over 3 weeks, Cisplatin, Carboplatin, 5Fluorouracil
Keywords
squamous cell carcinoma of the neck of unknown primary, HPV-Associated Oropharyngeal Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma, 17-409, Hypoxia negative, N1-2c oropharyngeal squamous cell carcinoma
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • F-FMISO PET/CT ScanDiagnostic test

    All subjects on Cohort A and the first 100 subjects accrued to Cohort B will undergo a pre-treatment F-FMISO scan PET/CT scan pretreatment. For both Cohort A and Cohort B, FMISO scan will be repeated between the 5th-10th RT day if pre-treatment scan is hypoxic. If the repeat 18F-FMISOscan PET/CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy. All subjects accrued onto Cohort B after 100 accruals will undergo only one 18F-FMISO scan done 5-10 treatment days after start of radiation therapy.

  • 30 Gy over 3 weeksRadiation

    Treatment will be delivered as one fraction per day on a standard 5 day per week schedule (excluding weekends and holidays), total of 30 Gy over 3 weeks at 2 Gy per fraction each day. The gross nodes, the primary/postoperative bed if applicable, all subclinical areas at risk for disease will receive the same dose at 30Gy.

  • CisplatinDrug

    Cycle 1 (week 1): At the start of week 1 of IMRT, subjects will receive cisplatin 100 mg/m2 intravenously. They may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 1 and 2, or as a single dose, typically on day 1.

  • CarboplatinDrug

    If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. Carboplatin will be given at a dose of AUC 1.25 intravenously daily x 4 days starting on day 1 of the cycle (total dose of AUC 5). Cycle 2 (Week 4): After the three weeks of radiation at week 4 when the subject no longer is receiving radiation therapy, subjects will receive cisplatin 100 mg/m2 intravenously. The may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 22 and 23, or as a single dose, typically on day 22.

  • 5FluorouracilDrug

    If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. 5-Fluorouracil will be given at a dose of 600 mg/m2 intravenous infusion over 24 hours daily x 4 days (total dose of 2400 mg/m2 intravenous infusion over 96 hours).

  • Proton TherapyRadiation

    Proton beam using pencil beam delivery either with the Varian or IBA delivery systems will be allowed for Cohort B. Proton beam therapy will be given at the New York Proton Center in New York City, where MSKCC has a well-established business associate agreement and cooperative research agreement with, respectively. If treatment at NYPC is not feasible, patients may be referred to ProCure in Somerset, NJ.

Study groups in NCT03323463
Study groupRoleWhat they receive
Arm A: HPV associated oropharyngeal carcinomaExperimentalHPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia. This arm is closed to accrual.
Receives: Diagnostic Test: F-FMISO PET/CT Scan; Radiation: 30 Gy over 3 weeks; Drug: Cisplatin; Drug: Carboplatin; Drug: 5Fluorouracil
Arm B: HPV associated oropharyngeal carcinomaExperimentalHPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia.
Receives: Diagnostic Test: F-FMISO PET/CT Scan; Radiation: 30 Gy over 3 weeks; Drug: Cisplatin; Drug: Carboplatin; Drug: 5Fluorouracil; Radiation: Proton Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effectiveness of study treatment for participants receiving de-escalated radiation therapy radiation therapy, comparable to participants treated with the current standard of care chemoradiation by standard CT (or MRI) or tumor site and PET scan

    The primary objective of this protocol is to demonstrate that the 2-year locoregional control for this cohort of subjects treated with a major de-escalated radiation dose of 30 Gy is not inferior to comparable subjects treated with the current standard chemoradiation at 70 GY by using a proportion test of patients who demonstrate 2-year locoregional control.

    Measured: 2 years (+/- 3 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2017
  2. Study start16 Oct 2017
  3. Primary completion31 Oct 2026 (estimated)
  4. Study completion31 Oct 2026 (estimated)

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
316 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03323463
Sponsor's protocol ID
17-409
Status last verified
Apr 2026
First submitted
17 Oct 2017
Last updated
13 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Undecided

Publications

  • Lee NY, Sherman EJ, Schoder H, Wray R, Boyle JO, Singh B, Grkovski M, Paudyal R, Cunningham L, Zhang Z, Hatzoglou V, Katabi N, Diplas BH, Han J, Imber BS, Pham K, Yu Y, Zakeri K, McBride SM, Kang JJ, Tsai CJ, Chen LC, Gelblum DY, Shah JP, Ganly I, Cohen MA, Cracchiolo JR, Morris LGT, Dunn LA, Michel LS, Fetten JV, Kripani A, Pfister DG, Ho AL, Shukla-Dave A, Humm JL, Powell SN, Li BT, Reis-Filho JS, Diaz LA, Wong RJ, Riaz N. Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma. J Clin Oncol. 2024 Mar 10;42(8):940-950. doi: 10.1200/JCO.23.01308. Epub 2024 Jan 19.

    PubMed 38241600

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing F-FMISO PET/CT Scan, 30 Gy over 3 weeks and Cisplatin in people with HPV-Associated Oropharyngeal Squamous Cell Carcinoma and Squamous Cell Carcinoma of the Neck, run by Memorial Sloan Kettering Cancer Center at 10 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 23 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effectiveness of study treatment for participants receiving de-escalated radiation therapy radiation therapy, comparable to participants treated with the current standard of care chemoradiation by standard CT (or MRI) or tumor site and PET scan (time frame: 2 years (+/- 3 months)). 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 NCT03323463, which also lists 1 linked publication.

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 13 Apr 2026.

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