Window of Opportunity in Preserving Laryngeal Function Trial
WOLF
A Phase II Window of Opportunity in Preserving Laryngeal Function (WOLF) Trial
1 other identifier
interventional
87
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2026
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 6, 2026
CompletedFirst Posted
Study publicly available on registry
February 20, 2026
CompletedStudy Start
First participant enrolled
April 6, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2031
April 13, 2026
April 1, 2026
3.1 years
February 6, 2026
April 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
At 1 year
Secondary Outcomes (4)
Overall Survival (OS)
Up to 5 years
Larynx preservation rate
Up to 5 years
Endoscopic evaluation of swallowing (FEES)
At Baseline, at 9 weeks, at 6 months after start of treatment, up to 1 year
Neck Dissection Impairment Index (NDII)
At Baseline, at every (21 day) treatment cycle, up to 1-year ± 14 days
Study Arms (3)
toripalimab + carboplatin + paclitaxel
EXPERIMENTALPrior 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.
Post-bioselection: Chemoradiation + toripalimab monotherapy
EXPERIMENTALPatients 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
Post-bioselection: Radiation + toripalimab monotherapy
EXPERIMENTALPatients 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
Interventions
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.
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.
\*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.
A chemotherapy drug that works by slowing or stopping cancer cell growth.
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.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Matthew Spectorlead
- Coherus Oncology, Inc.collaborator
Study Sites (1)
UPMC Hillman Cancer
Pittsburgh, Pennsylvania, 15213, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Spector, MD, FACS
UPMC Hillman Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor, Department of Otolaryngology-Head & Neck Surgery
Study Record Dates
First Submitted
February 6, 2026
First Posted
February 20, 2026
Study Start
April 6, 2026
Primary Completion (Estimated)
April 30, 2029
Study Completion (Estimated)
April 30, 2031
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share