Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M)Phase 2WOLFNCT07423078
Window of Opportunity in Preserving Laryngeal Function Trial
A Phase 2 study testing Toripalimab, Carboplatin and Cisplatin in people with Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M) and Locally Advanced Laryngeal Squamous Cell Carcinoma, run by Matthew Spector at 1 site in United States.
Trial summary
This trial will study the safety and tolerability and disease survival rates in adult patients with recurrent/metastatic (R/M) HNSCC when treated with carboplatin or cisplatin, paclitaxel, and toripalimab. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M), Locally Advanced Laryngeal Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma
- What is being tested?
- Toripalimab, Carboplatin and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Apr 2026to 30 Apr 2031
- Phase
- Phase 2
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
- Pathologically confirmed and previously untreated squamous cell carcinoma of the larynx or hypopharynx
- AJCC 8th Edition Stage III - IV disease (T1-T2/N1-N3, T3-T4/N0-N3)
- Disease (primary \& nodal) must be potentially surgically resectable and curable with conventional surgery and CRT
- ECOG PS 0 - 2
- Sexually active fertile subjects and their partners must agree to use highly effective method of contraception prior to study entry, during the course of the study, and for 1 year after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
- Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
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- Must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelet count ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 X the institutional upper limit of normal (ULN)
- AST (SGOT) ≤ 2.5 X institutional upper limit of normal (ULN)
- ALT (SGPT) ≤ 2.5 X institutional ULN
- Creatinine clearance ≥ 40 mL/min/1.73 m2 for patients with a creatinine level above institutional normal
- Must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior treatment for head and neck cancer
- Unresectable laryngeal or hypopharyngeal squamous cell carcinoma
- Distant metastatic disease
- Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism or Sjogren's syndrome will not be excluded from the study.
- Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
- Known allergy or hypersensitivity to carboplatin or cisplatin, toripalimab, or paclitaxel.
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- Prior malignancy within 2 years that in the investigator's opinion would be likely to affect the outcomes for the patient.
- Peripheral sensory neuropathy > grade 2 by CTCAE v5.0
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has acute or chronic active hepatitis B and C virus infection or known history of untreated hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA [qualitative]) or HIV infection (see note).
- Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.
- Note: Participants with a history of HIV infection are considered eligible if CD4+ T cell counts are ≥350 cells/µL and the patient has had no opportunistic infections in the last 12 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UPMC Hillman Cancer
Pittsburgh, Pennsylvania, 15213
Jennifer Ruth, RN, BSN, 412-623-8963, ruthj2@upmc.edu
Mel J Mendez, BS, 878-261-6071, mendezmj@upmc.edu
About this study
Official title: A Phase II Window of Opportunity in Preserving Laryngeal Function (WOLF) Trial
This trial will study the safety and tolerability and disease survival rates in adult patients with recurrent/metastatic (R/M) HNSCC when treated with carboplatin or cisplatin, paclitaxel, and toripalimab.
Read the detailed description
Currently, for patients with locally advanced laryngeal or hypopharyngeal squamous cell carcinoma (SCC), there is the option of total laryngectomy (TL) followed by adjuvant pathology driven therapy (RT or CRT) or an organ preservation approach. Total laryngectomy is a particularly morbid surgery, leaving a patient breathing through the neck for the rest of their life. In recent years however, upfront total laryngectomy with adjuvant RT has been in focus to growing concern of reduced overall survival rates in advanced laryngeal and hypopharyngeal SCC, particularly in patients with T4 disease. As such, upfront TL with adjuvant RT or CRT is typical, with organ preservation protocols more controversial, for T4 LSCC specifically. This trial provides neoadjuvant (chemo)immunotherapy (induction regimen of platinum (carboplatin or cisplatin), paclitaxel, and toripalimab) allowing for a novel approach to patient bioselection for the treatment of laryngeal cancer. Toripalimab is approved in combination with cisplatin and gemcitabine for the first-line treatment of patients with recurrent and/or metastatic nasopharyngeal carcinoma and has shown to significantly improved PFS and OS when combined with cisplatin and gemcitabine. Patients who show response to neoadjuvant therapy in laryngeal cancer have been shown to have 1) a better survival than patients who do not respond and 2) respond better to nonsurgical therapy. The addition of immunotherapy to chemotherapy has the potential to improve the response rate to neoadjuvant therapy, decrease the number of patients who require total laryngectomy as their primary treatment, and to improve the survival of patients with this highly morbid disease.
In October 2026, the "Endoscopic evaluation of swallowing (FEES)" outcome measure was updated, including the title of the outcome measure - now called "Prevalence of swallowing impairment". This change was made to align the record with a protocol modification that expanded the methods for assessing swallowing function beyond just FEES.
- Conditions
- Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M), Locally Advanced Laryngeal Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma
- Being tested
- Toripalimab, Carboplatin, Cisplatin, Paclitaxel, Radiation Therapy
- Keywords
- immunotherapy, laryngectomy, neoadjuvant
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called Loqtorzi
A monoclonal antibody (recombinant humanized programmed cell death protein 1 (PD-1) monoclonal antibody that acts as a checkpoint inhibitor) used for the treatment of melanoma and nasopharyngeal carcinoma.
CarboplatinDrug
Also called Paraplatin
A chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells.
CisplatinDrug
Also called Platinol, Platinol-AQ
*Can be used in place of carboplatin at the investigator's discretion. A chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells.
PaclitaxelDrug
Also called Taxol, Abraxane
A chemotherapy drug that works by slowing or stopping cancer cell growth.
Radiation TherapyRadiation
Also called intensity-modulated radiotherapy (IMRT)
Megavoltage energy photon beam irradiation. Any treatment planning and delivery system that has been credentialed for head and neck intensity-modulated radiotherapy (IMRT). Simultaneous integrated boost and sequential boost techniques (discretion of treating physician).
Total doses delivered to each Planning Target Volume (PTV) (in 33-35 fractions): High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60-63 Gy, Elective: 56-57 Gy
A sequential boost will consist of treatment of the combined PTVs 25 fractions followed by three sequential cone-downs targeting (Intermediate + Boost + High); (Boost + High); and High.
Total doses for the PTVs: High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60 Gy, Elective: 50 Gy.
| Study group | Role | What they receive |
|---|---|---|
| toripalimab + carboplatin + paclitaxel | Experimental | Prior to treatment:
Assessments include laryngoscopy and anatomic imaging studies
Treatment:
toripalimab 240mg IV with carboplatin (AUC 5) and paclitaxel (175 mg/m^2) IV every 3 weeks for two cycles. (Cisplatin 75mg/m^2 can be used in place of carboplatin at the investigator's discretion.)
After 2 Cycles of Treatment:
Repeat laryngoscopy and anatomic imaging studies. Undergo swallowing function and extranodal extension status assessment. Receives: Drug: Toripalimab; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel |
| Post-bioselection: Chemoradiation + toripalimab monotherapy | Experimental | Patients with PR ≥50% (not CR) with preserved swallowing function or CR, with preoperative N+ disease and extranodal extension upon neck dissection.
Induction Treatment: toripalimab 240mg IV+carboplatin (AUC 5)+paclitaxel (175 mg/m^2) IV Q
Continuation Treatment: toripalimab 240mg IV + carboplatin (AUC 5) + paclitaxel (175 mg/m^2) IV Q + Radiation therapy as per the Intervention Description + toripalimab 240mg IV monotherapy for 8 cycles Receives: Drug: Toripalimab; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy |
| Post-bioselection: Radiation + toripalimab monotherapy | Experimental | Patients with CR, with preoperative N0 disease or N+ disease with no extranodal extension upon neck dissection.
Induction Treatment: toripalimab 240mg IV+carboplatin (AUC 5)+paclitaxel (175 mg/m^2) IV Q
Continuation Treatment: Radiation therapy as per the Intervention Description + toripalimab 240mg IV monotherapy for 8 cycles Receives: Drug: Toripalimab; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-Year Disease-free survival (DFS)
Proportion of patients who have not experienced disease recurrence/progression or death from any cause at 1 year from start of treatment. Radiologic (CT or MRI) imaging as well as direct visualization by laryngoscopy will be used to assess disease with recurrence requiring a biopsy to be considered positive.
Measured: At 1 year
Secondary outcomes (4)
Overall Survival (OS)
Median time from initiation of study therapy to death from any cause.
Measured: Up to 5 years
Larynx preservation rate
The proportion of responding patients (without disease recurrence/progression or death from any cause) who do not undergo laryngectomy during the study period. Radiologic (CT or MRI) imaging as well as direct visualization by laryngoscopy will be used to assess disease with recurrence requiring a biopsy to be considered positive.
Measured: Up to 5 years
Prevalence of swallowing impairment
The proportion of participants with swallowing impairment. Swallowing impairment may be evaluated by flexible endoscopic examination of swallowing (FEES), modified barium swallow (MBS), or another method at the discretion of the treating physician. The physician will indicate the presence or absence of impairment of the pharynx and/or larynx that effects swallowing at each stated timepoint.
Measured: At baseline, at 3 weeks after completion of induction therapy, at 6 months into the treatment continuation period, and at 1 year into the treatment continuation period. Total timeframe of data collection up to 14.5 months from start of induction therapy.
Neck Dissection Impairment Index (NDII)
Patient Reported Outcome Measure (PROM) is a 10-item, self-report instrument. A 5-level Likert scale is used for responses ranging from 'not at all' = 10 to 'a lot' = 0 related to pain/discomfort and limitation of movement as a result of cancer treatment. The NDII scores range from 0 to 100, with higher scores indicating better shoulder functioning and quality of life (QOL). Factors such as age, weight, radiation treatment, and neck dissection type significantly affect the QOL score.
Measured: At Baseline, at every (21 day) treatment cycle, up to 1-year ± 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start6 Apr 2026
- Primary completion30 Apr 2029 (estimated)
- Study completion30 Apr 2031 (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 Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M)Studies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Matthew Spector
- Sponsor type
- University, hospital or other
- Collaborators
- Coherus Oncology, Inc.
- Responsible party
- Sponsor-investigator, Matthew Spector, University of Pittsburgh
- Investigators
- Matthew Spector, MD, FACS, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07423078
- Sponsor's protocol ID
- HCC 25-126
- Acronym
- WOLF
- Status last verified
- Oct 2026
- First submitted
- 6 Feb 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No