Lattice-Based Radiotherapy and Chemoimmunotherapy for Oropharyngeal Squamous Cell Carcinoma

NCT07428148 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-00211
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm Phase I/II trial evaluates induction chemoimmunotherapy combined with lattice radiotherapy (LRT) in patients with non-low risk oropharyngeal squamous cell carcinoma and primary tumor ≥3 cm or primary tumor and pathologic lymph node ≥3 cm in longest dimension. BOIN12 adaptive dose-finding will guide dose across two anatomical cohorts-primary-tumor only (P) and primary + largest involved node (PN)-with a total target accrual of about 60 evaluable patients. Dose-limiting toxicity is monitored separately in each cohort. If both tolerate the same dose, that unified optimal biological dose (OBD) advances to Phase II; if tolerability differs, the PN-specific OBD expands while the P cohort is analyzed descriptively. After induction, imaging determines response: patients achieving ≥50% volumetric tumor shrinkage receive hypofractionated chemoradiation, whereas those with \<50% shrinkage are treated with conventional fractionation, personalizing definitive therapy according to early safety and efficacy signals.

Conditions

Oropharyngeal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting-toxicity (DLT) rate

  Phase I only - measured as the percentage of participants with DLTs during the initial treatment window.

  Up to Day 21

• Proportion of patients with ≥ 50 % volumetric tumor shrinkage after induction therapy

  Phase II only - proportion of patients who achieve at least 50 % volumetric tumor shrinkage after induction therapy.

  Up to Month 24

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Up to Month 24

• Overall Survival (OS)

  Up to Month 24

• Distant Metastasis-Free Survival

  Up to Month 24

• Proportion of Patients with Change in CPS ≥20

  Up to Month 24

Study Arms (8)

(Cohort P) Phase I: 8 Gy Dose

EXPERIMENTAL

Individuals in the primary tumor only (P) cohort enrolled in Phase 1 who receive the 8 Gray (Gy) dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort PN) Phase I: 8 Gy Dose

EXPERIMENTAL

Individuals in the primary + node (NP) cohort enrolled in Phase 1 who receive the 8 Gy dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort P) Phase I: 16 Gy Dose

EXPERIMENTAL

Individuals in the primary tumor only (P) cohort enrolled in Phase 1 who receive the 16 Gy dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort PN) Phase I: 16 Gy Dose

EXPERIMENTAL

Individuals in the primary + node (NP) cohort enrolled in Phase 1 who receive the 16 Gy dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort P) Phase I: 24 Gy Dose

EXPERIMENTAL

Individuals in the primary tumor only (P) cohort enrolled in Phase 1 who receive the 24 Gy dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort PN) Phase I: 24 Gy Dose

EXPERIMENTAL

Individuals in the primary + node (NP) cohort enrolled in Phase 1 who receive the 24 Gy dose.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort P) Phase II: OBD

EXPERIMENTAL

Individuals in Cohort P who receive the optimal biological dose (OBD) for Cohort P as determined by BOIN12 in Phase I.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

(Cohort PN) Phase II: OBD

EXPERIMENTAL

Individuals in Cohort PN who receive the optimal biological dose (OBD) for Cohort PN as determined by BOIN12 in Phase I.

Drug: Induction Chemo-Immunotherapy; Radiation: Lattice Radiotherapy

Interventions

Induction Chemo-Immunotherapy DRUG

All participants will receive three 21-day cycles of carboplatin, paclitaxel, and pembrolizumab as induction therapy.

(Cohort P) Phase I: 16 Gy Dose; (Cohort P) Phase I: 24 Gy Dose; (Cohort P) Phase I: 8 Gy Dose; (Cohort P) Phase II: OBD; (Cohort PN) Phase I: 16 Gy Dose; (Cohort PN) Phase I: 24 Gy Dose; (Cohort PN) Phase I: 8 Gy Dose; (Cohort PN) Phase II: OBD

Lattice Radiotherapy RADIATION

On Day 1 of the first cycle, each participant also begins lattice radiotherapy (LRT). Cohort P receives LRT to the primary tumor only; Cohort NP receives LRT to the primary tumor + involved lymph nodes ≥ 3 cm.

(Cohort P) Phase I: 16 Gy Dose; (Cohort P) Phase I: 24 Gy Dose; (Cohort P) Phase I: 8 Gy Dose; (Cohort P) Phase II: OBD; (Cohort PN) Phase I: 16 Gy Dose; (Cohort PN) Phase I: 24 Gy Dose; (Cohort PN) Phase I: 8 Gy Dose; (Cohort PN) Phase II: OBD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the oropharynx, which includes the sites tonsil, base of tongue, soft palate, or posterior oropharyngeal wall. Histologic variants will be included (papillary squamous cell carcinoma and basaloid squamous cell carcinoma). Cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx.
• Clinical stage T1-T4, N1-N3, M0
• If tissue is positive for p16 by immunohistochemical staining (\>70% staining), patient must have \>10 pk-year smoking history
• Zubrod Performance Status of 0-1
• Primary tumor ≥ 3 cm OR at least one lymph node ≥ 3 cm OR primary tumor and lymph node ≥ 3 cm
• One of the following combinations of imaging is required within 8 weeks of registration: CT scan of the neck (with contrast) and a whole body PET/CT; or, an MRI of the neck (with contrast) and a whole body PET/CT. Note: A CT scan of the neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools.
• Patients must provide their personal smoking history prior to registration. Patients with HPV positive oropharyngeal carcinoma must have a cumulative personal smoking history that exceeds 10 pack-years. Number of pack-years = \[Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)\] / 20. Note: Twenty cigarettes is considered equivalent to one pack. Cigar and pipe tobacco consumption is not included in calculating lifetime pack-years.
• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy. Female subjects of childbearing potential who are undergoing RT or who are partners to male subjects in the study should avoid sexual activity or use a highly effective method of birth control during sexual intercourse. Acceptable, highly effective methods of birth control include: intrauterine device (IUD)/intrauterine hormone releasing system (IUS), bilateral tube occlusion, vasectomized partner, combined (estrogen and progesterone containing) or progesterone-only hormonal contraceptives (oral, intravaginal, transdermal, injectable).
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (abstinence/protection) for the duration of treatment/study participation.
• The patient must provide study-specific informed consent prior to study entry.
• Adequate renal function within 2 weeks 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 Cockcorft-Gault formula.
• Adequate hematologic function within 2 weeks prior to registration, defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Platelets ≥ 100,000 cells/mm3; and Hemoglobin ≥ 8.0 g/dl. Note: the use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
• Patients who are HIV positive but who have no prior AIDS-defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
• The patient must provide study-specific informed consent prior to study entry.

You may not qualify if:

• Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive;
• Carcinoma of the neck of unknown primary site origin (even if p16 positive)
• Distant metastasis or adenopathy below the clavicles;
• Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease.
• Simultaneous primary cancers or separate bilateral primary tumor sites;
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
• 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 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; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those listed in 5.1.
• Acquired immune deficiency syndrome (AIDS) based upon the current CDC definition with immune compromise greater than that noted in section 5.1; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immune-compromised patients.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Kenneth Hu, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kenneth Hu, MD

CONTACT

212-731-5003; kenneth.hu@nyulangone.org

Fraustina Hsu

CONTACT

cancertrials@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2026
• First Posted: February 23, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2033
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)