Neoadjuvant Chemoimmunotherapy Followed By Radiation Or Organ Preservation Surgery In Laryngeal/Hypopharyngeal Cancer

NCT06039631 | Recruiting Phase 2 DMC

• 1 other identifier: Larynx-IO 2.0
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

In the global landscape of cancer, head and neck malignancies are highly prevalent, with 878,000 new cases and 444,000 deaths recorded in 2020. Notably, laryngeal and hypopharyngeal cancers contribute to around 30% of these instances. More than 50% of patients are diagnosed with locally advanced disease, necessitating intensive treatments that significantly impact their quality of life. Despite these efforts, the prognosis for laryngeal and hypopharyngeal cancers remains grim, with a 5-year survival rate of 30% to 50%. Past approaches focused on preserving laryngeal function and patient well-being, including minimally invasive surgery, advanced radiotherapy, and induction chemotherapy. Our prior research highlighted the effectiveness of combining toripalimab-based induction therapy and chemotherapy, followed by concurrent chemoradiotherapy or surgery. Positive short-term outcomes and manageable side effects were observed, with encouraging larynx preservation rates after one year. Against this backdrop, the current study aims to explore neoadjuvant immunotherapy combined with chemotherapy for patients with locally advanced laryngeal and hypopharyngeal cancer. It seeks to compare the therapeutic efficacy and quality of life impacts of concurrent radiochemotherapy and organ-preserving surgery. The ultimate goal is to identify optimal strategies for future interventions.

Conditions

Larynx Cancer; Hypopharyngeal Cancer

Keywords

organ preservation; PD-1 inhibitor; Immunotherapy; Neoadjuvant chemotherapy; Induction chemotherapy; larynx presrvation surgery

Outcome Measures

Primary Outcomes (1)

• Progression-free survival rate

  Progression-free survival is defined as the time interval from the commencement of randomization until the first documented occurrence of objective tumor progression or death due to any cause, whichever comes first.

  At two year post-randomization

Secondary Outcomes (4)

• Larynx Preservation rate

  At two year post-randomization

• Overall Survival rate

  At two year post-randomization

• Quality of life

  From enrollment to two year post-randomization

• Adverse events

  From enrollment to two year post-randomization

Study Arms (2)

Organ preservation surgery

EXPERIMENTAL

In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended, and the specific surgical approach will be chosen based on individual case characteristics and the treatment protocols followed at our center. Depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

Procedure: Surgery; Radiation: Radiation; Drug: Toripalimab

Concurrent chemoradiation

OTHER

In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin. Starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

Radiation: Radiation; Drug: Toripalimab

Interventions

Surgery PROCEDURE

In the surgical group, patients will undergo curative surgery for laryngeal/hypopharyngeal cancer along with cervical lymph node dissection. Organ preservation surgery is recommended.

Organ preservation surgery

Radiation RADIATION

In the surgical group, depending on postoperative pathology results, adjuvant radiotherapy or concurrent radiochemotherapy may be administered as deemed necessary. If postoperative pathology indicates extracapsular invasion of lymph nodes or positive surgical margins, concurrent radiochemotherapy based on cisplatin is recommended. In the concurrent radiochemotherapy group, patients will undergo target delineation based on the scope before induction chemotherapy. Radiotherapy will be administered at a total dose of 70 Gy over 35 fractions, and concurrent chemotherapy will involve weekly administration of cisplatin at a dosage of 30 mg/m².

Concurrent chemoradiation; Organ preservation surgery

Toripalimab DRUG

In the both groups, starting three weeks after the completion of radiotherapy, patients will receive adjuvant immunotherapy using a specific protocol of toripalimab at a dose of 240 mg every 3 weeks for a total of 8 cycles.

Concurrent chemoradiation; Organ preservation surgery

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signing of the informed consent form and willingness to comply with the study protocol.
• Age ≥18 and ≤75 years.
• Histologically confirmed laryngeal or hypopharyngeal squamous cell carcinoma.
• Locally advanced laryngeal/hypopharyngeal cancer patients eligible for surgical resection (AJCC 8th edition stage: T2N+M0, T3-T4aN0-3M0).
• Presence of at least one measurable lesion before treatment, in accordance with RECIST 1.1 criteria for "measurable lesions."
• Patients who have received neoadjuvant immunotherapy combined with chemotherapy and have achieved a partial response (PR) in the primary lesion according to RECIST 1.1 criteria and are suitable candidates for organ preservation surgery.
• Expected survival of more than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Good organ function, meeting the following criteria:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L.
• Platelet count ≥100×10\^9/L.
• Hemoglobin ≥9 g/dL.
• Serum albumin ≥2.8 g/dL.
• Total bilirubin ≤1.5× upper limit of normal (ULN), ALT, AST, and/or ALP ≤3× ULN.
• Serum creatinine ≤1.5× ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula, see Appendix III).

You may not qualify if:

• History of allergic reactions to any components of toripalimab, paclitaxel, or cisplatin.
• Pre-existing tracheostomy due to laryngeal dysfunction before treatment.
• Uncontrolled clinical cardiac symptoms or diseases, including:
• NYHA Class II or higher heart failure.
• Unstable angina.
• Myocardial infarction within the past year.
• Clinically significant ventricular or supraventricular arrhythmias requiring clinical intervention.
• Previous treatment with any of the following:
• Use of any investigational drug within 4 weeks prior to the first dose of study treatment.
• Concurrent participation in another clinical trial, unless it is an observational (non-interventional) clinical trial.
• Requiring systemic treatment with corticosteroids (daily dose \>10 mg prednisone equivalent) or other immunosuppressive medications within 2 weeks prior to the first dose of study treatment, excluding corticosteroids for localized inflammation or prophylaxis against allergies or nausea/vomiting. Other specific circumstances should be discussed with the investigator. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal replacement therapy with a dose of \>10 mg/day prednisone or equivalent are allowed.
• Vaccination with anti-tumor vaccines or administration of live vaccines within 4 weeks prior to the first dose of study treatment (for patients who received COVID-19 vaccine, a 2-week interval is required).
• Major surgery within 4 weeks before the first dose of study treatment or presence of severe trauma.
• Failure to recover to ≤ Grade 1 toxicity per CTCAE (except for alopecia and residual neuropathy related to prior platinum therapy) from previous cancer therapy or from any other cause unrelated to study/enrollment criteria.
• Active autoimmune disease or history of autoimmune disease, such as interstitial lung disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes. However, stable dose of thyroid replacement therapy for autoimmune-mediated hypothyroidism is allowed. Stable dose of insulin for type I diabetes is allowed. Patients with vitiligo or childhood-onset asthma/allergies requiring no intervention as adults are allowed.

Sponsors & Collaborators

• Fudan University: lead
• Fudan University Eye Ear Nose and Throat Hospital: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: collaborator
• Ruijin Hospital: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Laryngeal Neoplasms; Hypopharyngeal Neoplasms

Interventions

Surgical Procedures, Operative; Radiation; toripalimab

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Chair

Model Details: the selection trial design

Study Record Dates

• First Submitted: September 9, 2023
• First Posted: September 15, 2023
• Study Start: August 22, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After the pubilcation of this study and the approvement of IRB, till two years after pubilcation.
• Access Criteria: The data will be assessed via contact with principal investigator.

Locations

CN (1)