Response-Adaptive Treatment in Untreated Locoregional HPV-Negative Head and Neck Cancer

NCT07065630 | Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB25-0567
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the objective response rate following neoadjuvant therapy with volrustomig, paclitaxel, and carboplatin in previously untreated human papillomavirus (HPV)-negative locally advanced head and neck squamous cell carcinoma .

Conditions

Head and Neck Cancer; HPV

Outcome Measures

Primary Outcomes (1)

• Response rate

  Assess the objective response rate following neoadjuvant therapy with volrustomig, paclitaxel, and carboplatin in previously untreated human papillomavirus (HPV)-negative locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The proportion of patients who achieve an objective response (30% or greater tumor shrinkage per RECIST v1.1 criteria) after chemoimmunotherapy.

  24 months

Secondary Outcomes (4)

• Survival outcomes

  24 months

• Control of treatment failure

  24 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  24 months

• Patterns of treatment failure

  24 months

Study Arms (3)

Volrustomig

EXPERIMENTAL

Dose Level 0: 500 mg IV on day 1 of 21-day cycle Dose Level 1: 750 mg IV on day 1 of 21-day cycle After the completion of radiation, patients will be initiated on maintenance volrustomig. Volrustomig will be administered at 250mg on day 1 of a 21-day cycle for 12 cycles (36 weeks/9 months)

Drug: Volrustomig

Carboplatin (AUC)

EXPERIMENTAL

Dose Level 0: AUC 5 IV on day 1 of 21-day cycle Dose Level 1: AUC 5 IV on day 1 of 21-day cycle

Drug: Carboplatin

Paclitaxel (mg/m2)

EXPERIMENTAL

Dose Level 0: 100 mg/m2 IV on Day 1 and Day 8 of 21-day cycle Dose Level 1: 100 mg/m2 IV on Day 1 and Day 8 of 21-day cycle

Drug: Paclitaxel

Interventions

Volrustomig DRUG

500mg or 750mg (cycles 1-2) and 250mg thereafter IV day 1.

Volrustomig

Carboplatin DRUG

100mg/m2 IV day 1 and day 8.

Carboplatin (AUC)

Paclitaxel DRUG

AUC 5 IV day 1

Paclitaxel (mg/m2)

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed locally advanced, non-metastatic, head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, or sinuses.
• If a primary oropharyngeal squamous cell carcinoma is diagnosed, HPV must be ruled out by immunohistochemistry (defined as negative immunohistochemical staining of p16)
• Non-oropharyngeal primary sites do not require immunohistochemical or other means of testing for HPV status, however if they are performed, must be negative for HPV.
• Nasopharyngeal primary must have both EBV and HPV ruled out by immunohistochemistry to be eligible.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Stage IV disease with the exception of nasopharyngeal primary T3N2 (stage III) based of AJCC staging 8th edition.
• Patients must have measurable disease per RECIST 1.1 criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• No previous radiation, chemotherapy, or immunotherapy for a head and neck cancer.
• Age ≥18 years.
• ECOG performance status of 0 or 1.
• Patients must have adequate organ and marrow function as defined below
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥ 1.5 × 109/L (1,500 per mm3)
• Platelet count ≥ 100 × 109/L (100,000 per mm3)

You may not qualify if:

• Unequivocal demonstration of distant metastatic disease (M1 disease).
• Unidentifiable primary site.
• Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment as discussed above.
• Patients who are receiving any other investigational agents.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years. Exceptions include other cancers that have undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to volrustomig or other agents used in study.
• Patients with uncontrolled intercurrent illness.
• Negative pregnancy test (urine or serum) for female subjects of childbearing potential. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of volrustomig to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used. Pregnant women are excluded from this study because volrustomig is an anti-PD1/anti-CTLA4 agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with volrustomig, breastfeeding should be discontinued if the mother is treated with volrustomig. These potential risks may also apply to other agents used in this study.
• Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Volrustomig monotherapy.
• Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of Volrustomig to prevent pregnancy in a partner.
• Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival. This includes but is not limited to ongoing or active infection, immunodeficiency, specified cardiac conditions (below), pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Patients with clinically stable and/or chronically managed medical illnesses that are not symptomatic and/or are not expected to impact treatment on protocol are still eligible.
• Any of the following cardiac conditions:
• Cardiomyopathy of any etiology or history of myocarditis
• Heart failure (as defined by New York Heart Association class III-IV)
• Uncontrolled hypertension

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

Clinical Trials Intake

CONTACT

855-702-8222; cancerclinicaltrials@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: July 15, 2025
• Study Start: October 7, 2025
• Primary Completion (Estimated): August 13, 2029
• Study Completion (Estimated): August 13, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)