Locally Advanced Hypopharyngeal CarcinomaPhase 2NCT06151743
Neoadjuvant PD-1 Inhibitor Combined With Cetuximab and Platinum in Resectable Locally Advanced Hypopharyngeal Carcinoma
A Phase 2 study testing three cycles (toripalimab + cetuximab + platinum), Radical surgery and Radiotherapy or chemoradiotherapy in people with Locally Advanced Hypopharyngeal Carcinoma, run by Eye & ENT Hospital of Fudan University at 1 site in China.
Trial summary
The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Hypopharyngeal Carcinoma
- What is being tested?
- three cycles (toripalimab + cetuximab + platinum), Radical surgery and Radiotherapy or chemoradiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 18 Jan 2024to 1 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed as hypopharyngeal squamous cell carcinoma;
- Age between 18-75 years;
- Patients with resectable locally advanced hypopharyngeal cancer with T3-4aN0-3bM0 (AJCC 8th) require total laryngectomy;
- Have at least one evaluable target lesion according to RECIST 1.1 criteria.
- No previous treatment for hypopharyngeal carcinoma;
- Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;
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- Estimated survival ≥ 6 months;
- Normal organ function;
- HBV DNA < 500 IU/mL (or 2500 copies/mL) and HCV RNA negative;
- Signed informed consent;
- Patients who are compliant, willing, and able to follow visiting schedules, treatment plans, laboratory tests, and other research procedures.
- Male and no pregnant female; able to use the contraceptive method during treatment.
Who cannot join
- Have a history of other cancers in the past five years, except for the following cancers that are cured in the past five years: basal cell carcinoma and squamous cell carcinoma of the skin, early prostate cancer, papillary thyroid cancer, breast ductal carcinoma in situ and cervix carcinoma in situ;
- The target lesion has been treated with radiation therapy or surgery, except for biopsy to confirm the diagnosis of hypopharyngeal carcinoma;
- Previous chemotherapy, immunotherapy, or bio-targeted therapy for the primary tumor;
- Patients who have participated in other clinical trials within four weeks before the trial;
- Any of the following diseases within six months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
- Those with hypertension who cannot be reduced to normal range by antihypertensive drugs (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
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- Patients with grade I or above coronary heart disease, arrhythmia (including QTc interval prolongation > 450 ms for men and > 470 ms for women), and cardiac insufficiency.
- Patients with positive urine protein (urine protein test 2 + or above, or 24-hour urine protein quantification >1.0g).
- Patients with severe allergic history or allergic constitution; an active autoimmune disease that may worsen when receiving immunostimulants. Patients with type I diabetes, vitiligo, psoriasis, or diseases of hypothyroidism or hyperthyroidism that do not require immunosuppressive therapy are eligible to participate in the study.
- Subjects requiring systemic therapy with corticosteroids (> 10 mg prednisone or equivalent) or other immunosuppressants within two weeks before the first use of the study drug.
- Previously diagnosed immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) - related disease. hepatitis B virus (HBV) surface antigen positive and HBV-DNA ≥ 500 IU/mL (or 2500 copies/mL), or HCV RNA positive. History of active or previous tuberculosis (TB).
- Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders.
- Vaccination within four weeks before enrollment, except for inactivated vaccine.
- Pregnant or lactating women, those who are in the reproductive period and do not use effective contraception;
- Those whom the investigator deems unsuitable to participate in this trial, such as severe acute or chronic medical conditions (including immune colitis, inflammatory bowel disease, non-infectious pneumonia, pulmonary fibrosis) or psychiatric illness (including recent or active suicidal ideation or behavior) or abnormal laboratory tests.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Eye & ENT Hospital of Fudan University
Shanghai, Shanghai Municipality, 200031
+86 02164376425
About this study
Official title: Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer
The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Participants will receive three cycles of TPC neoadjuvant therapy (toripalimab+ cetuximab + platinum), radical surgery (laryngeal preservation surgery if possible), and sequential (chemo)radiotherapy treatment after surgery. This trial aims to answer the following questions:
- pCR rate
- MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years
- Safety and quality of life
Read the detailed description
The standard treatment for patients with resectable hypopharyngeal carcinoma is surgery plus postoperative adjuvant radiotherapy or chemoradiotherapy. Growing evidence shows that neoadjuvant therapy may significantly increase pCR in locally advanced SCCHN patients, potentially improving patient survival. The development of drugs, immunotherapy, and targeted therapy has been proven to improve the overall survival of patients with SCCHN significantly, and PD-1 inhibitor combined with cetuximab has also shown promising efficacy in R/M SCCHN. This study explores the effectiveness and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal carcinoma.
- Being tested
- three cycles (toripalimab + cetuximab + platinum), Radical surgery, Radiotherapy or chemoradiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
three cycles (toripalimab + cetuximab + platinum)Drug
Also called Toripalimab + Cetuximab + Platinum
Cetuximab 250 mg/m2 i.v. qw (first loading dose 400 mg/m2) for nine doses; Toripalimab 240 mg/m2 i.v. d1, q21d, three cycles; Cisplatin 25 mg/m2 i.v. d1-3, q21d, three cycles or Carboplatin AUC 5 i.v. d1, q21d, three cycles (patients with cisplatin contraindications or renal impairment after cisplatin use).
Radical surgeryProcedure or surgery
The attending physician should select the appropriate surgical treatment and try to perform radical laryngeal preservation surgery for patients with tumor retraction after induction therapy. Patients who cannot preserve laryngeal function due to tumor load need to undergo total laryngeal resection. According to the scope of pharyngectomy, the surgical treatments include partial laryngopharyngectomy, total laryngectomy and partial pharyngectomy, total laryngopharyngectomy, and total pharyngo-laryngo-esophagectomy. Cervical lymph node dissection was performed when necessary.
Radiotherapy or chemoradiotherapyRadiation
- Using intensity-modulated radiotherapy (IMRT) technology, the dose of radiotherapy is determined according to whether there are adverse prognostic factors in the postoperative pathology, including positive margins, extracapsular invasion of lymph nodes, primary pT3 or T4, N2 lymph node lesions, peripheral nerve invasion, vascular/lymphatic infiltration. Primary site: residual GTV or tumor bed dose 60-70Gy: 1.8-2.12 Gy / fraction. Cervical lymph nodes or lymphatic drainage area: 56-70 Gy: 1.7-2.12 Gy / fraction.
- Postoperative adjuvant concurrent chemotherapy regimen:
Cisplatin 25mg/m2 i.v. d1-3, d22-24 or Carboplatin AUC 5 i.v. d1, d22 (if cisplatin contraindications).
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant therapy+Surgery+Adjuvant therapy | Experimental | Participants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation. Receives: Drug: three cycles (toripalimab + cetuximab + platinum); Procedure: Radical surgery; Radiation: Radiotherapy or chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rate after neoadjuvant chemotherapy
The pCR rate is defined as the percentage of participants who have no residual tumor cells in the resected primary tumor within 14 weeks after the start of neoadjuvant therapy.
Measured: Within 3 weeks after surgery
Secondary outcomes (6)
Major pathologic response (MPR) rate
MPR rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists.
Measured: Within 3 weeks after surgery
Objective response rate (ORR) after neoadjuvant therapy
The ORR is the proportion of patients whose tumor volume was reduced to 30% and sustained for more than 4 weeks as assessed by RECIST 1.1.
Measured: Up to 14 weeks after the start of neoadjuvant therapy
1-year and 2-year larynx preservation rate (LPR)
LPR is the proportion of patients who avoid total laryngectomy. 1-year and 2-year LPR is defined as the probability of larynx preservation for a patient at a given time (1 year and 2 years).
Measured: Two years post-radiotherapy
1-year and 2-year disease-free survival (DFS) rate
DFS is the time from enrollment until radiographic disease progression, local or distant recurrence, or death due to any cause. The 1-year and 2-year DFS rate is the probability of disease-free survival for a patient at a given time (1 year and 2 years).
Measured: Two years post-radiotherapy
1-year and 2-year overall survival (OS) rate
OS is the time from enrollment to death due to any cause. The 1-year and 2-year OS rates are the probability of overall survival for a patient at a given time (1 year and 2 years).
Measured: Two years post-radiotherapy
Adverse Effect
Adverse Effect, evaluated by CTCAE V5.0
Measured: One year post-radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2023
- Study start18 Jan 2024
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Hypopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Eye & ENT Hospital of Fudan UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eye & ENT Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lei Tao, Principal investigator, Eye & ENT Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06151743
- Sponsor's protocol ID
- TPC-SCCHN
- Status last verified
- Nov 2023
- First submitted
- 22 Nov 2023
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Therapy With Toripalimab Combined With Cetuximab and Platinum for Resectable Locally Advanced Hypopharyngeal Cancer
- ClinicalTrials.gov ID
- NCT06151743
- Acronym / sponsor ID
- TPC-SCCHN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Eye & ENT Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- 18 Jan 2024 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 30 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical trial is to evaluate the efficacy and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal cancer. Participants will receive three cycles of TPC neoadjuvant therapy (toripalimab+ cetuximab + platinum), radical surgery (laryngeal preservation surgery if possible), and sequential (chemo)radiotherapy treatment after surgery. This trial aims to answer the following questions:
- pCR rate
- MPR rate, ORR, LPR/DFS/OS rare at 1 and 2 years
- Safety and quality of life
Detailed description
The standard treatment for patients with resectable hypopharyngeal carcinoma is surgery plus postoperative adjuvant radiotherapy or chemoradiotherapy. Growing evidence shows that neoadjuvant therapy may significantly increase pCR in locally advanced SCCHN patients, potentially improving patient survival. The development of drugs, immunotherapy, and targeted therapy has been proven to improve the overall survival of patients with SCCHN significantly, and PD-1 inhibitor combined with cetuximab has also shown promising efficacy in R/M SCCHN. This study explores the effectiveness and safety of immunotherapy combined with cetuximab and platinum neoadjuvant therapy in patients with resectable locally advanced hypopharyngeal carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant therapy+Surgery+Adjuvant therapy | Experimental | Drug: three cycles (toripalimab + cetuximab + platinum), Procedure: Radical surgery, Radiation: Radiotherapy or chemoradiotherapyParticipants receive three cycles of neoadjuvant therapy (toripalimab+cetuximab+platinum), followed by radical surgery. After surgery, participants receive radiotherapy or chemoradiotherapy according to the pathological results of the operation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Pathologically confirmed as hypopharyngeal squamous cell carcinoma;
- Age between 18-75 years;
- Patients with resectable locally advanced hypopharyngeal cancer with T3-4aN0-3bM0 (AJCC 8th) require total laryngectomy;
- Have at least one evaluable target lesion according to RECIST 1.1 criteria.
- No previous treatment for hypopharyngeal carcinoma;
Key exclusion criteria (15 listed)
- Have a history of other cancers in the past five years, except for the following cancers that are cured in the past five years: basal cell carcinoma and squamous cell carcinoma of the skin, early prostate cancer, papillary thyroid cancer, breast ductal carcinoma in situ and cervix carcinoma in situ;
- The target lesion has been treated with radiation therapy or surgery, except for biopsy to confirm the diagnosis of hypopharyngeal carcinoma;
- Previous chemotherapy, immunotherapy, or bio-targeted therapy for the primary tumor;
- Patients who have participated in other clinical trials within four weeks before the trial;
- Any of the following diseases within six months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| three cycles (toripalimab + cetuximab + platinum)Also: Toripalimab + Cetuximab + PlatinumCetuximab 250 mg/m2 i.v. qw (first loading dose 400 mg/m2) for nine doses; Toripalimab 240 mg/m2 i.v. d1, q21d, three cycles; Cisplatin 25 mg/m2 i.v. d1-3, q21d, three cycles or Carboplatin AUC 5 i.v. d1, q21d, three cycles (patients with cisplatin contraindications or renal impairment after cisplatin use). | Drug | Neoadjuvant therapy+Surgery+Adjuvant therapy |
| Radical surgeryThe attending physician should select the appropriate surgical treatment and try to perform radical laryngeal preservation surgery for patients with tumor retraction after induction therapy. Patients who cannot preserve laryngeal function due to tumor load need to undergo total laryngeal resection. According to the scope of pharyngectomy, the surgical treatments include partial laryngopharyngectomy, total laryngectomy and partial pharyngectomy, total laryngopharyngectomy, and total pharyngo-laryngo-esophagectomy. Cervical lymph node dissection was performed when necessary. | Procedure or surgery | Neoadjuvant therapy+Surgery+Adjuvant therapy |
| Radiotherapy or chemoradiotherapy1. Using intensity-modulated radiotherapy (IMRT) technology, the dose of radiotherapy is determined according to whether there are adverse prognostic factors in the postoperative pathology, including positive margins, extracapsular invasion of lymph nodes, primary pT3 or T4, N2 lymph node lesions, peripheral nerve invasion, vascular/lymphatic infiltration. Primary site: residual GTV or tumor bed dose 60-70Gy: 1.8-2.12 Gy / fraction. Cervical lymph nodes or lymphatic drainage area: 56-70 Gy: 1.7-2.12 Gy / fraction. 2. Postoperative adjuvant concurrent chemotherapy regimen: Cisplatin 25mg/m2 i.v. d1-3, d22-24 or Carboplatin AUC 5 i.v. d1, d22 (if cisplatin contraindications). | Radiation | Neoadjuvant therapy+Surgery+Adjuvant therapy |
Primary outcome
Pathological complete response (pCR) rate after neoadjuvant chemotherapy
Time frame: Within 3 weeks after surgery
The pCR rate is defined as the percentage of participants who have no residual tumor cells in the resected primary tumor within 14 weeks after the start of neoadjuvant therapy.
6 secondary outcomes
Major pathologic response (MPR) rate
Time frame: Within 3 weeks after surgery
Objective response rate (ORR) after neoadjuvant therapy
Time frame: Up to 14 weeks after the start of neoadjuvant therapy
1-year and 2-year larynx preservation rate (LPR)
Time frame: Two years post-radiotherapy
1-year and 2-year disease-free survival (DFS) rate
Time frame: Two years post-radiotherapy
1-year and 2-year overall survival (OS) rate
Time frame: Two years post-radiotherapy
Adverse Effect
Time frame: One year post-radiotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lei Tao principal investigator
Eye & ENT Hospital of Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing three cycles (toripalimab + cetuximab + platinum), Radical surgery and Radiotherapy or chemoradiotherapy in people with Locally Advanced Hypopharyngeal Carcinoma, run by Eye & ENT Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lei Tao, PhD (13916944810, doctortaolei@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (pCR) rate after neoadjuvant chemotherapy (time frame: Within 3 weeks after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024.