Head and Neck CancerPhase 2SAVERNCT04609280
Selective Avoidance of Nodal VolumEs at Minimal Risk (GCC 20110)
A Phase 2 study testing Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT) in people with Head and Neck Cancer and Oropharynx Cancer, run by University of Maryland, Baltimore at 6 sites in United States.
Trial summary
This is a phase II, non-randomized, therapeutic trial with the primary objective to determine the efficacy of reduced contralateral (C/L) elective nodal treatment volumes in preventing C/L recurrences at 2 years in patients with p16 positive oropharyngeal squamous cell carcinoma undergoing definitive or adjuvant RT. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Oropharynx Cancer, Oropharyngeal Squamous Cell Carcinoma
- What is being tested?
- Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 6 sitesUnited States
- Study dates
- 1 Mar 2021to Dec 2027
- 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
- Is there pathologically (histologically or cytologically) proven diagnosis of p16+ squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil or base of tongue)? Note: Cytologic diagnosis from a cervical lymph node (from a paraffin block, not from smears) is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage).
- Does the patient require elective contralateral radiotherapy in the definitive or adjuvant setting (i.e. base of tongue primary or tonsil with base of tongue invasion, soft palate invasion, or medialized as defined by > 1/3 of the distance from the tonsil to the midline of the soft palate?
- Does the patient have clinical stage T1-4, N0, N1 or N3, and M0 disease (AJCC 8th edition) as defined by physical examination and appropriate imaging (PET/CT preferred, CT neck with IV contrast with CT chest without contrast as recommended alternative to PET/CT)?
- Was a general history and physical examination performed by a radiation oncologist, medical oncologist, or head and neck surgeon within 60 days prior to registration?
- Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?
- Is the patient ≥ 18 years of age?
Show all 10Show fewer
- For women of childbearing potential, was a serum pregnancy test completed within 2 weeks of initiation or radiotherapy?
- If yes, was the serum pregnancy test negative?
- If a woman of child-bearing potential or sexually active male, is the patient willing to use effective contraception throughout their participation in the treatment phase of the study and at least 180 days following the last study treatment.
- Did the patient provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required p16 review?
Who cannot join
- Does the patient have cancer considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx?
- Does the patient have a carcinoma of the neck of unknown primary origin?
- Does the patient have distant metastasis?
- Does the patient have prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years?
- Did the patient have prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)?
- Did the patient have prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields?
Show all 11Show fewer
- Did the patient have prior surgery of the head and neck excluding superficial removal of cutaneous skin malignancies?
- Is the patient homeless?
- Does the patient have an active drug or alcohol dependency?
- Is the patient pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)?
- Radiographic evidence of contralateral nodal disease as described below. 1) Max standardized uptake value (SUV) greater than 3.0, or 2) Short-axis diameter is > 1.5 cm for level II nodes, > 0.8 cm for retropharyngeal node, or > 1.0 cm for level III, IV, or V, or 3) Central necrosis or heterogeneous enhancement
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Maryland Proton Treatment Center
Baltimore, Maryland, 21201
UMMC
Baltimore, Maryland, 21201
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
Upper Chesapeake Health
Bel Air, Maryland, 21014
Central Maryland Radiation Oncology
Columbia, Maryland, 21044
Baltimore Washington Medical Center
Glen Burnie, Maryland, 21061
About this study
Official title: A Single-arm, Single-stage Phase II Trial of Selective Avoidance of Nodal VolumEs at Minimal Risk (SAVER) in the Contralateral Neck of Patients With p16-positive Oropharynx Cancer
This is a phase II, non-randomized, therapeutic trial with the primary objective to determine the efficacy of reduced contralateral (C/L) elective nodal treatment volumes in preventing C/L recurrences at 2 years in patients with p16 positive oropharyngeal squamous cell carcinoma undergoing definitive or adjuvant RT.
Read the detailed description
Patients with human papillomavirus (HPV) or its surrogate marker p16, positive oropharyngeal squamous cell carcinoma (p16+OPSCC) exhibit favorable overall survival (OS) rates of 70-100% at 3 years. These outcomes are dependent on disease burden and patient characteristics and independent of treatment modality. Significant treatment related side effects exist despite advances in radiotherapy (RT) technology, surgical techniques, and supportive care. In addition to common acute toxicities, the favorable OS of patients with p16+OPSCC potentially places them at increased risk for developing long-term treatment-induced side-effects. Therefore, it is important to establish novel management approaches that maintain excellent current clinical outcomes while effectively reducing acute and long-term side effects.
One such approach of limiting RT-induced toxicity is to decrease the amount of normal tissue that receives radiation through judicious reduction of RT treatment volumes. Treatment of elective nodal volumes increases dose to numerous organs at risk (OARs). Patients with well-lateralized tonsil tumors and limited neck disease can effectively be treated with ipsilateral nodal radiotherapy. However, based on recent phase III trials, contralateral (C/L) elective nodal radiation is performed for the majority of patients with p16+OPSCC increasing acute and long-term toxicities. Therefore, judicious data-driven approaches for decreasing the number of elective ipsilateral and contralateral nodal levels treated is necessary to limit RT-induced side effects. This protocol tests the hypothesis that treating only the high-risk sub-volumes of levels II and III would be effective in maintaining regional control in the elective neck while decreasing xerostomia (dry mouth) and dysphagia (swallowing difficulties).
- Being tested
- Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT)
- Keywords
- Head and Neck Cancer, Oropharynx Cancer, Oropharyngeal Squamous Cell Carcinoma, Radiotherapy, Proton Therapy, Photon Therapy
- Medical subject headings
- Head and Neck Neoplasms, Oropharyngeal Neoplasms, 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.
Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT)Radiation
Delivered over 6 weeks in 30 daily fractions in the adjuvant setting and over 6.5 weeks in 33 daily fractions in the definitive setting. In the adjuvant setting, areas with positive surgical margins or nodal stations with pathologic extranodal extension will receive 63 Gy. Margin negative resection bed and involved nodal stations without extranodal extension will receive 54 Gy. Low-risk elective nodal volumes (i.e. ceCTV) will receive 51 Gy. In the definitive setting, gross disease will receive 69.96 Gy, areas at high-risk for subclinical disease will receive 60 Gy, and areas at low-risk for harboring subclinical disease (i.e. ceCTV) will receive 52.8 Gy.
| Study group | Role | What they receive |
|---|---|---|
| Reduced C/L elective nodal volume | Experimental | All patients will receive the reduced C/L elective nodal volume as described. Treatment will be delivered via IMRT/VMAT or PBPT. Receives: Radiation: Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Elective out-of-field contralateral nodal failure
Time to failure will be calculated from the date of informed consent until the date of nodal failure in the untreated elective neck sub-volume.
Measured: 2-years following completion of radiotherapy
Secondary outcomes (7)
Grade 2/3 xerostomia
defined by PRO-CTCAE (patient-reported outcome (PRO) measurement system - Common Terminology Criteria for Adverse Events (CTCAE))
Measured: 2-years following completion of radiotherapy
Dysphagia using The M.D. Anderson Dysphagia Inventory (MDADI)
The M.D. Anderson Dysphagia Inventory is a self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the Quality of Life (QOL) of patients with head and neck cancer.
Measured: 2-years following completion of radiotherapy
PEG-tube rate
Percutaneous endoscopic gastrostomy (PEG)-tube rate
Measured: 2-years following completion of radiotherapy
Overall survival
Measured: 2-years following completion of radiotherapy
Progression-free survival
Measured: 2-years following completion of radiotherapy
Locoregional control
Measured: 2-years following completion of radiotherapy
Incidence of pulmonary metastases
Measured: 2-years following completion of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2020
- Study start1 Mar 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies 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
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Department of Radiation Oncology, University of Maryland, Baltimore
- Investigators
- Matthew Witek, MD, Principal investigator, University of Maryland/Maryland Proton Treatment Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04609280
- Sponsor's protocol ID
- HP-00093439
- Acronym
- SAVER
- Status last verified
- Aug 2026
- First submitted
- 23 Oct 2020
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Single-stage Phase II Trial of Selective Avoidance of Nodal VolumEs at Minimal Risk (SAVER) in the Contralateral Neck of Patients With p16-positive Oropharynx Cancer
- ClinicalTrials.gov ID
- NCT04609280
- Acronym / sponsor ID
- SAVER / HP-00093439
- Keywords
- Head and Neck Cancer, Oropharynx Cancer, Oropharyngeal Squamous Cell Carcinoma, Radiotherapy, Proton Therapy, Photon Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 30 Oct 2020 (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.
This is a phase II, non-randomized, therapeutic trial with the primary objective to determine the efficacy of reduced contralateral (C/L) elective nodal treatment volumes in preventing C/L recurrences at 2 years in patients with p16 positive oropharyngeal squamous cell carcinoma undergoing definitive or adjuvant RT.
Detailed description
Patients with human papillomavirus (HPV) or its surrogate marker p16, positive oropharyngeal squamous cell carcinoma (p16+OPSCC) exhibit favorable overall survival (OS) rates of 70-100% at 3 years. These outcomes are dependent on disease burden and patient characteristics and independent of treatment modality. Significant treatment related side effects exist despite advances in radiotherapy (RT) technology, surgical techniques, and supportive care. In addition to common acute toxicities, the favorable OS of patients with p16+OPSCC potentially places them at increased risk for developing long-term treatment-induced side-effects. Therefore, it is important to establish novel management approaches that maintain excellent current clinical outcomes while effectively reducing acute and long-term side effects.
One such approach of limiting RT-induced toxicity is to decrease the amount of normal tissue that receives radiation through judicious reduction of RT treatment volumes. Treatment of elective nodal volumes increases dose to numerous organs at risk (OARs). Patients with well-lateralized tonsil tumors and limited neck disease can effectively be treated with ipsilateral nodal radiotherapy. However, based on recent phase III trials, contralateral (C/L) elective nodal radiation is performed for the majority of patients with p16+OPSCC increasing acute and long-term toxicities. Therefore, judicious data-driven approaches for decreasing the number of elective ipsilateral and contralateral nodal levels treated is necessary to limit RT-induced side effects. This protocol tests the hypothesis that treating only the high-risk sub-volumes of levels II and III would be effective in maintaining regional control in the elective neck while decreasing xerostomia (dry mouth) and dysphagia (swallowing difficulties).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reduced C/L elective nodal volume | Experimental | Radiation: Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT)All patients will receive the reduced C/L elective nodal volume as described. Treatment will be delivered via IMRT/VMAT or PBPT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Is there pathologically (histologically or cytologically) proven diagnosis of p16+ squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil or base of tongue)? Note: Cytologic diagnosis from a cervical lymph node (from a paraffin block, not from smears) is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage).
- Does the patient require elective contralateral radiotherapy in the definitive or adjuvant setting (i.e. base of tongue primary or tonsil with base of tongue invasion, soft palate invasion, or medialized as defined by > 1/3 of the distance from the tonsil to the midline of the soft palate?
- Does the patient have clinical stage T1-4, N0, N1 or N3, and M0 disease (AJCC 8th edition) as defined by physical examination and appropriate imaging (PET/CT preferred, CT neck with IV contrast with CT chest without contrast as recommended alternative to PET/CT)?
- Was a general history and physical examination performed by a radiation oncologist, medical oncologist, or head and neck surgeon within 60 days prior to registration?
- Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?
Key exclusion criteria (11 listed)
- Does the patient have cancer considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx?
- Does the patient have a carcinoma of the neck of unknown primary origin?
- Does the patient have distant metastasis?
- Does the patient have prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years?
- Did the patient have prior systemic chemotherapy for the study cancer (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 |
|---|---|---|
| Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT)Delivered over 6 weeks in 30 daily fractions in the adjuvant setting and over 6.5 weeks in 33 daily fractions in the definitive setting. In the adjuvant setting, areas with positive surgical margins or nodal stations with pathologic extranodal extension will receive 63 Gy. Margin negative resection bed and involved nodal stations without extranodal extension will receive 54 Gy. Low-risk elective nodal volumes (i.e. ceCTV) will receive 51 Gy. In the definitive setting, gross disease will receive 69.96 Gy, areas at high-risk for subclinical disease will receive 60 Gy, and areas at low-risk for harboring subclinical disease (i.e. ceCTV) will receive 52.8 Gy. | Radiation | Reduced C/L elective nodal volume |
Primary outcome
Elective out-of-field contralateral nodal failure
Time frame: 2-years following completion of radiotherapy
Time to failure will be calculated from the date of informed consent until the date of nodal failure in the untreated elective neck sub-volume.
7 secondary outcomes
Grade 2/3 xerostomia
Time frame: 2-years following completion of radiotherapy
Dysphagia using The M.D. Anderson Dysphagia Inventory (MDADI)
Time frame: 2-years following completion of radiotherapy
PEG-tube rate
Time frame: 2-years following completion of radiotherapy
Overall survival
Time frame: 2-years following completion of radiotherapy
Progression-free survival
Time frame: 2-years following completion of radiotherapy
Locoregional control
Time frame: 2-years following completion of radiotherapy
Incidence of pulmonary metastases
Time frame: 2-years following completion of radiotherapy
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 12 Aug 2026.
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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. This study is not recruiting at the moment.
Matthew Witek, MD principal investigator
University of Maryland/Maryland Proton Treatment Center
6 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 Intensity modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) or Pencil beam proton therapy (PBPT) in people with Head and Neck Cancer and Oropharynx Cancer, run by University of Maryland, Baltimore at 6 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 10 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: under way, not looking for participants, as of the sponsor's last update on 12 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 6 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?
Elective out-of-field contralateral nodal failure (time frame: 2-years following completion of radiotherapy). 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 12 Aug 2026; AzTrials last refreshed its copy on 26 Oct 2026.