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Head and Neck Cancer Squamous Cell CarcinomaPhase 2INITIUMNCT07773987

Immunotherapy and Nodal-Sparing Irradiation for T-Cell Induction and Unmasking of Tumor Antigenicity in the Microenvironment for Head and Neck Cancer

A Phase 2 study testing Pembrolizumab, Radiotherapy and ENI in people with Head and Neck Cancer Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a non-comparative randomized Phase 2 study using the INITIUM regimen with or without elective nodal irradiation (ENI) delivered before surgery for resectable head and neck squamous cell carcinoma (HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Radiotherapy and ENI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
8 Oct 2026to Oct 2029
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

  • Patients 18 years or older.
  • Patients with surgically resectable squamous cell carcinoma of the oral cavity or HPV-negative squamous cell carcinoma of the oropharynx. Resectability will be determined by the treating surgeon. Patients must have locoregionally advanced disease defined by clinical T3-4 staging and/or clinical node positive staging.
  • A CPS score of at least 1 on initial biopsy.
  • Zubrod, or Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Pregnancy. It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
  • Female patients must meet one of the following:
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  • Postmenopausal for at least one year before the screening visit, OR
  • Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
  • If subject is of childbearing potential (defined as not satisfying either of the above two criteria):
  • Agree to practice two effective methods of contraception (combination methods requires use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive, intrauterine device, etonogestrel implant, etc.) from the time of signing of the informed consent form through 90 days after the last dose of study agent, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable contraception methods).
  • Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
  • Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
  • Must also adhere to the guidelines of any study-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post ovulation methods] and withdrawal are not acceptable methods of contraception.) - Ability to understand a written informed consent document, and the willingness to sign it.

Who cannot join

  • HPV-positive squamous cell carcinoma of the oropharynx.
  • Tumor inaccessible for clinic-based biopsy as determined by the treating surgeon.
  • Solid organ transplant requiring chronic immunosuppression.
  • Autoimmune disease requiring use of steroids or chronic immunosuppression.
  • Prior invasive malignancy within the past 3 years (except for T1a surgically treated melanoma with negative margins, any early-stage non-melanomatous skin cancer, early-stage prostate cancer, or differentiated thyroid cancer). Patients with benign non-metastasizing tumors are eligible.
  • Life expectancy less than 12 months.
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  • Performance status Zubrod ≥ 3.
  • Patients with prior external beam radiation therapy (RT) to the head and neck that overlaps the expected treatment fields.
  • Note: Patients receiving prior Iodine-131 therapy will be eligible.
  • Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.
  • Body weight ≤ 30 kg.
  • Any of the following severe laboratory abnormalities within 30 days of registration, unless corrected prior to it:
  • Sodium < 125 mmol/L or > 155 mmol/L
  • Potassium < 3.5 mmol/L or > 6 mmol/L
  • Glucose > 400 mg/dl
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl
  • Magnesium < 0.9 mg/dl or > 3 mg/dl
  • Unstable angina and/or congestive heart failure requiring hospitalization within three months of registration.
  • Transmural myocardial infarction within three months of registration.
  • Medical or psychiatric illness that would compromise the patient's ability to tolerate treatment or limit compliance with study requirements.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after radiation. This exclusion is necessary because the treatment involved in this study may be significantly teratogenic. Women who are breastfeeding are also excluded.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Medical College of Wisconsin Cancer Center Clinical Trials Office contact

866-680-0505 ext. 8900

cccto@mcw.edu

United States1 site, 1 recruiting

  • Froedtert & the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Musaddiq Awan, MD, 414-805-4400 ext. mawan@mcw.edu

    Recruiting

Other trials in United States

About this study

This is a non-comparative randomized Phase 2 study using the INITIUM regimen with or without elective nodal irradiation (ENI) delivered before surgery for resectable head and neck squamous cell carcinoma (HNSCC).

Read the detailed description

Patients with surgically resectable HPV-negative HNSCC with no prior history of head and neck radiation and a life expectancy of at least 12 months will be enrolled.

Patients will undergo pre-radiation pembrolizumab for two cycles followed by pre-operative radiotherapy and two additional cycles of pembrolizumab. Radiation will be given to a total dose of 35 Gy in 5 fractions to gross disease, followed by response-directed surgery approximately eight weeks after completion of radiation. Patients randomized to ENI will concurrently receive 27 Gy in 5 fractions to elective nodal regions during radiation to gross disease.

Baseline symptom evaluation will be obtained using validated surveys for head and neck cancer patients: the Functional Assessment of Cancer Therapy for the Head and Neck (FACT-HN) and the MD Anderson Dysphagia Inventory for Head and Neck (MDADI-HN). Tumor biopsies will be performed serially across treatment for translational study at the following time points: baseline, after induction pembrolizumab, on the final day of radiation, and at the time of surgery. If patients sign a secondary consent, quantitative MRI (qMRI) will be performed prior to radiation, on the day of the last fraction of radiation and six weeks after the completion of radiation, prior to surgery.

Being tested
Pembrolizumab, Radiotherapy, ENI, Surgery
Keywords
elective nodal irradiation, immunotherapy

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    All patients will undergo induction with pembrolizumab (200 mg) given intravenously every three weeks for two cycles prior to radiation and two cycles after radiation.

  • RadiotherapyRadiation

    All patients will receive 7 Gy daily for 5 fractions to gross disease.

  • ENIRadiation

    Patients receiving ENI will be treated to 5.4 Gy daily to the elective nodal basins for 5 fractions concurrent with treatment to gross disease.

  • SurgeryProcedure or surgery

    Patients will be scheduled for surgery at ten weeks (-7 days) after radiation to allow for maximal tumor regression and healing of any radiation-related mucositis. Surgical resection will be tailored to the treatment response.

Study groups in NCT07773987
Study groupRoleWhat they receive
INITIUM regimen using ENIExperimentalThe INITIUM regimen includes two cycles of induction therapy with pembrolizumab, followed by pre-operative hypofractionated radiation (7 Gy × 5 fractions) and two additional cycles of pembrolizumab. Patients will receive ENI to non-clinically and radiographically involved draining nodal basins.
Receives: Drug: Pembrolizumab; Radiation: Radiotherapy; Radiation: ENI; Procedure: Surgery
INITIUM regimen without ENIExperimentalThe INITIUM regimen includes two cycles of induction therapy with pembrolizumab, followed by pre-operative hypofractionated radiation (7 Gy × 5 fractions) and two additional cycles of pembrolizumab. Patients will NOT receive ENI to non-clinically and radiographically involved draining nodal basins.
Receives: Drug: Pembrolizumab; Radiation: Radiotherapy; Procedure: Surgery

What is being measured

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

  1. Pathologic complete response (pCR) rate to INITIUM-HN with and without ENI.

    pCR is defined as no viable tumor in primary tumor or lymph nodes on pathological examination.

    Measured: Up to 10 weeks post-radiation therapy

Timeline

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

  1. First posted19 Aug 2026
  2. Study start8 Oct 2026
  3. Primary completionOct 2029 (estimated)
  4. Study completionOct 2029 (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
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07773987
Sponsor's protocol ID
PRO00059024
Acronym
INITIUM
Status last verified
Oct 2026
First submitted
12 Aug 2026
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Radiotherapy and ENI in people with Head and Neck Cancer Squamous Cell Carcinoma, run by Medical College of Wisconsin at 1 site 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 16 inclusion and 21 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 19 Oct 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 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 Medical College of Wisconsin Cancer Center Clinical Trials Office (866-680-0505 ext. 8900, cccto@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic complete response (pCR) rate to INITIUM-HN with and without ENI. (time frame: Up to 10 weeks post-radiation therapy). 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 NCT07773987.

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 19 Oct 2026.

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