Squamous Cell Carcinoma of Head and NeckPhase 3NCT06647563
Neoadjuvant Toripalimab + Chemotherapy ± Cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma (Neo-ICT)
A Phase 3 study testing Toripalimab, Cetuximab and Albumin-Bound Paclitaxel in people with Squamous Cell Carcinoma of Head and Neck, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.
Trial summary
This study is a randomized, active-controlled, open-label clinical trial for participants with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one control arm. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- Toripalimab, Cetuximab and Albumin-Bound Paclitaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 355 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2024to 30 Sep 2030
- Phase
- Phase 3
- 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
- Histologically confirmed squamous cell carcinoma of the head and neck (excluding nasopharyngeal cancer);
- Male or female, aged 18-75 years;
- Clinical stage III-IVb (AJCC 8th edition TNM stage) and operable patients; if oropharyngeal squamous cell carcinoma (P16-), the stage is III-IVb; if oropharyngeal squamous cell carcinoma (P16+), the stage is III;
- No prior antitumor therapy including radiotherapy, chemotherapy, immunotherapy or biological therapy for the current tumor;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
- Life expectancy ≥ 6 months;
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- No obvious contraindications to immunotherapy, radiochemotherapy, or surgical treatment;
- Willing to accept surgical treatment;
- The level of main organ function meets the following criteria:
- Routine blood tests: WBC ≥ 4.0 × 10^9/L, ANC ≥ 1.5 × 10^9/L, PLT ≥ 100 × 10^9/L, Hb ≥ 90 g/L (no blood transfusion or blood products within 14 days, no correction with G-CSF and other hematopoietic growth factors);
- Biochemical assessments: serum albumin ≥ 3.0 g/dL (30 g/L), TBIL ≤ 1.5 × ULN, ALT, AST ≤ 2.5 × ULN, BUN and CRE ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula);
- Adequate coagulation function: defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; If the subject is receiving anticoagulant therapy, PT should be within the proposed therapeutic range of the anticoagulant;
- Women of childbearing potential must have a negative pregnancy test result (serum or urine), conducted within seven days prior to enrollment and agree to use effective contraception during the study period and for six months post last dose of anti-PD-1 antibody administration. Male subjects with female partners who are capable of conception must also utilize effective contraception throughout this study duration and for six months after their final dose anti-PD-1 antibody;
- Willingness to participate in this study by signing an informed consent form, while exhibiting strong compliance and readiness to cooperate with follow-up procedures.
Who cannot join
- Previous treatment with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody, or other drugs/antibodies targeting T cell co-stimulation or checkpoint pathway;
- Active autoimmune disease. Subjects in stable condition who do not require systemic immunosuppressive therapy are permitted; examples include type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not necessitate systemic treatment (e.g., vitiligo, psoriasis, alopecia).
- Patients with congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml) or hepatitis C (positive antibody for HCV, and HCV-RNA above the lower limit of detection of the analytical procedure);
- Known allergy to the study drug or any of its excipients; or serious allergic reaction to other monoclonal antibodies.
- The occurrence of any of the following conditions within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, NYHA class II or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure.
- Vaccination with live vaccines within 4 weeks prior to the first dose of the study drug. Inactivated virus vaccine can be administered for seasonal flu, but not attenuated live influenza vaccines administered intranasally.
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- Known history of allogeneic organ transplant or allogeneic stem cell transplant.
- The history of drug addiction and the abuse of psychoactive substances.
- Pregnant or breastfeeding women.
- Any other malignant neoplasm diagnosed within 5 years prior to study entry, except for carcinoma that is amenable to local treatment and has been cured, such as basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, carcinoma in situ of breast ductal, and papillary thyroid cancer.
- Patients with other significant physical or mental health conditions, or laboratory test abnormalities that may elevate the risk of participation in the study or compromise the integrity of the study results, as determined by the investigators, are deemed unsuitable for participation in this study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Randomized Controlled Study of Toripalimab Combined With Chemotherapy or With Chemotherapy/Cetuximab as Neoadjuvant Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Neo-ICT)
This study is a randomized, active-controlled, open-label clinical trial for participants with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one control arm. Participants in Experimental Arm A will receive two cycles of Toripalimab, albumin-bound paclitaxel, carboplatin, and cetuximab prior to surgery. Participants in Experimental Arm B will receive two cycles of Toripalimab, albumin-bound paclitaxel, and carboplatin before surgical intervention. Following the surgical procedure, individuals in both Experimental Arm A and B will continue to receive 15 cycles of Toripalimab. The Control Arm will undergo the current standard treatment without preoperative drug intervention. Postoperatively, participants will be administered postoperative radiotherapy or chemoradiotherapy based on their recurrence risk. The primary study hypotheses are that the treatments in the Experimental Arms will improve the 2-year event-free survival (EFS) rates compared to the standard control treatment.
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Being tested
- Toripalimab, Cetuximab, Albumin-Bound Paclitaxel, Carboplatin, Cisplatin
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Head and Neck Squamous Cell Carcinoma, Toripalimab, Albumin-bound paclitaxel, Carboplatin, Cetuximab, Neoadjuvant
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabBiological
Also called PD-1 antibody
Specified dose on specified days
CetuximabBiological
Also called EGFR antibody
Specified dose on specified days
Albumin-Bound PaclitaxelDrug
Specified dose on specified days
CarboplatinDrug
Specified dose on specified days
CisplatinDrug
Specified dose on specified days
Radiotherapy 60 Gray/dayRadiation
Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.
Radiotherapy 66 Gray/dayRadiation
High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.
Radiotherapy 70 Gray/dayRadiation
Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT) | Experimental | Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1, and Cetuximab 400mg/m^2 on Day 1, followed by Cetuximab 250mg/m^2 on Day 1 of each subsequent week. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. Receives: Biological: Toripalimab; Biological: Cetuximab; Drug: Albumin-Bound Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day |
| Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) | Experimental | Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. Receives: Biological: Toripalimab; Drug: Albumin-Bound Paclitaxel; Drug: Carboplatin; Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day |
| No Neoadjuvant + SOC (Control) | Active comparator | Participants will receive the standard of care (SOC) with no neoadjuvant prior to surgery. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Receives: Drug: Cisplatin; Radiation: Radiotherapy 60 Gray/day; Radiation: Radiotherapy 66 Gray/day; Radiation: Radiotherapy 70 Gray/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
ICT vs Control: Two-Year Event-free Survival (EFS) rate
Two-Year Event-free Survival (EFS) rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Two-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.
Measured: Up to ~72 months
IC vs Control: Two-Year EFS rate
Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Two-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.
Measured: Up to ~72 months
Secondary outcomes (20)
ICT vs Control: Overall Survival (OS)
OS is the time from randomization to death due to any cause. Per protocol, OS in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
IC vs Control: OS
OS is the time from randomization to death due to any cause. Per protocol, OS in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
ICT vs IC: Major Pathological Response (MPR)
The percentage of participants with a major pathological response (MPR) as assessed by the Central Pathologist at the time of definitive surgery. MPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
Per protocol, MPR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~40 months
ICT vs IC: Pathological Complete Response (PCR)
he percentage of participants with a pathological complete response (PCR) as assessed by the central pathologist at the time of definitive surgery. PCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.
Per protocol, PCR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~40 months
ICT vs IC: Objective Response Rate (ORR)
According to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Objective Response Rate (ORR) assesses the proportion of subjects with complete response (CR) and partial response (PR).
Per RECIST v1.1 criteria for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Per protocol, ORR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~40 months
ICT vs Control: Three-Year EFS rate
Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Three-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~84 months
ICT vs Control: Five-Year EFS rate
Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Five-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
IC vs Control: Three-Year EFS rate
Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Three-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~84 months
IC vs Control: Five-Year EFS rate
Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Five-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
ICT vs IC: Two-Year EFS rate
Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Two-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~72 months
ICT vs IC: Three-Year EFS rate
Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Three-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~84 months
ICT vs IC: Five-Year EFS rate
Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm.
EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death.
EFS: The time from randomization, until the first documented occurrence of EFS event.
Per protocol, Five-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
ICT vs IC vs Control: Locoregional recurrence-free survival (LRFS) rate
The Two-Year, Three-Year, and Five-Year LRFS rates refer to the proportions of participants who have not experienced locoregional recurrence and are still alive at 2, 3, and 5 years post-randomization, respectively, out of all participants in the arm.
Per protocol, the LRFS rate will be compared between the ICT, IC, and Control arms.
Measured: Up to ~96 months
ICT vs IC vs Control: Distant Disease-free Survival (DDFS) rate
Two-Year, Three-Year, and Five-Year DDFS rates refer to the proportion of patients who have not experienced distant metastasis and are still alive at 2, 3, and 5 years post-randomization, out of all participants in the arm.
Per protocol, the DDFS rate will be compared between the ICT, IC, and Control arms.
Measured: Up to ~96 months
ICT vs IC vs Control: Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL)
Change from baseline in the combined score of global health status (GHS)/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 29 and 30. Participant responses to questions regarding overall health/QoL will be scored on a 7-point scale (1=Very poor to 7=Excellent) with a higher score indicating better overall health status.
Measured: Up to ~96 months
ICT vs IC vs Control: Change From Baseline in Global Health Status/Physical Functioning Scales
Change from baseline in the combined score of physical functioning scale using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 1 through 5. Participant responses to questions regarding their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much) with a higher score indicating worse physical functioning.
Measured: Up to ~96 months
ICT vs IC vs Control: Change from Baseline in Swallowing, Speech, and Pain Symptoms
Change from baseline in the combined score of swallowing, speech, and pain symptoms using the European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (EORTC QLQ-H\&N35) items 31-38, 46, and 53-54. Participant responses to questions regarding problems with swallowing, speech and pain in the mouth will be scored on a 4-point scale (1=Not at all to 4=Very much) with a higher score indicating more problems.
Measured: Up to ~96 months
ICT vs IC vs Control: Percentage of Participants Experiencing An Adverse Event (AEs)
Percentage of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
Measured: Up to ~96 months
ICT vs IC: Percentage of Participants Discontinuing Study Drug Due to AEs
Percentage of participants discontinuing study drug due to an AE.
Measured: Up to ~48 months
ICT vs IC: OS
OS is the time from randomization to death due to any cause. Per protocol, OS in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population.
Measured: Up to ~96 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 355 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yue He, MD, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
- Investigators
- Yue He, M.D., Principal investigator, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06647563
- Sponsor's protocol ID
- JYKQ-2024-105
- Status last verified
- Oct 2024
- First submitted
- 13 Oct 2024
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study of Toripalimab Combined With Chemotherapy or With Chemotherapy/Cetuximab as Neoadjuvant Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Neo-ICT)
- ClinicalTrials.gov ID
- NCT06647563
- Acronym / sponsor ID
- JYKQ-2024-105
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Head and Neck Squamous Cell Carcinoma, Toripalimab, Albumin-bound paclitaxel, Carboplatin, Cetuximab, Neoadjuvant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 355 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 18 Oct 2024 (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.
This study is a randomized, active-controlled, open-label clinical trial for participants with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one control arm. Participants in Experimental Arm A will receive two cycles of Toripalimab, albumin-bound paclitaxel, carboplatin, and cetuximab prior to surgery. Participants in Experimental Arm B will receive two cycles of Toripalimab, albumin-bound paclitaxel, and carboplatin before surgical intervention. Following the surgical procedure, individuals in both Experimental Arm A and B will continue to receive 15 cycles of Toripalimab. The Control Arm will undergo the current standard treatment without preoperative drug intervention. Postoperatively, participants will be administered postoperative radiotherapy or chemoradiotherapy based on their recurrence risk. The primary study hypotheses are that the treatments in the Experimental Arms will improve the 2-year event-free survival (EFS) rates compared to the standard control treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT) | Experimental | Biological: Toripalimab, Biological: Cetuximab, Drug: Albumin-Bound Paclitaxel, Drug: Carboplatin, Drug: Cisplatin, Radiation: Radiotherapy 60 Gray/day, Radiation: Radiotherapy 66 Gray/day, Radiation: Radiotherapy 70 Gray/dayParticipants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1, and Cetuximab 400mg/m^2 on Day 1, followed by Cetuximab 250mg/m^2 on Day 1 of each subsequent week. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. |
| Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) | Experimental | Biological: Toripalimab, Drug: Albumin-Bound Paclitaxel, Drug: Carboplatin, Drug: Cisplatin, Radiation: Radiotherapy 60 Gray/day, Radiation: Radiotherapy 66 Gray/day, Radiation: Radiotherapy 70 Gray/dayParticipants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. |
| No Neoadjuvant + SOC (Control) | Active comparator | Drug: Cisplatin, Radiation: Radiotherapy 60 Gray/day, Radiation: Radiotherapy 66 Gray/day, Radiation: Radiotherapy 70 Gray/dayParticipants will receive the standard of care (SOC) with no neoadjuvant prior to surgery. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically confirmed squamous cell carcinoma of the head and neck (excluding nasopharyngeal cancer);
- Male or female, aged 18-75 years;
- Clinical stage III-IVb (AJCC 8th edition TNM stage) and operable patients; if oropharyngeal squamous cell carcinoma (P16-), the stage is III-IVb; if oropharyngeal squamous cell carcinoma (P16+), the stage is III;
- No prior antitumor therapy including radiotherapy, chemotherapy, immunotherapy or biological therapy for the current tumor;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
Key exclusion criteria (11 listed)
- Previous treatment with anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody, or other drugs/antibodies targeting T cell co-stimulation or checkpoint pathway;
- Active autoimmune disease. Subjects in stable condition who do not require systemic immunosuppressive therapy are permitted; examples include type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not necessitate systemic treatment (e.g., vitiligo, psoriasis, alopecia).
- Patients with congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml) or hepatitis C (positive antibody for HCV, and HCV-RNA above the lower limit of detection of the analytical procedure);
- Known allergy to the study drug or any of its excipients; or serious allergic reaction to other monoclonal antibodies.
- The occurrence of any of the following conditions within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, NYHA class II or higher cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure.
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 |
|---|---|---|
| ToripalimabAlso: PD-1 antibodySpecified dose on specified days | Biological | Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| CetuximabAlso: EGFR antibodySpecified dose on specified days | Biological | Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT) |
| Albumin-Bound PaclitaxelSpecified dose on specified days | Drug | Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| CarboplatinSpecified dose on specified days | Drug | Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| CisplatinSpecified dose on specified days | Drug | No Neoadjuvant + SOC (Control), Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| Radiotherapy 60 Gray/dayLow risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy. | Radiation | No Neoadjuvant + SOC (Control), Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| Radiotherapy 66 Gray/dayHigh risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy. | Radiation | No Neoadjuvant + SOC (Control), Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
| Radiotherapy 70 Gray/dayParticipants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy. | Radiation | No Neoadjuvant + SOC (Control), Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT), Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) |
Primary outcome
ICT vs Control: Two-Year Event-free Survival (EFS) rate
Time frame: Up to ~72 months
Two-Year Event-free Survival (EFS) rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.
IC vs Control: Two-Year EFS rate
Time frame: Up to ~72 months
Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population.
20 secondary outcomes
ICT vs Control: Overall Survival (OS)
Time frame: Up to ~96 months
IC vs Control: OS
Time frame: Up to ~96 months
ICT vs IC: Major Pathological Response (MPR)
Time frame: Up to ~40 months
ICT vs IC: Pathological Complete Response (PCR)
Time frame: Up to ~40 months
ICT vs IC: Objective Response Rate (ORR)
Time frame: Up to ~40 months
ICT vs Control: Three-Year EFS rate
Time frame: Up to ~84 months
ICT vs Control: Five-Year EFS rate
Time frame: Up to ~96 months
IC vs Control: Three-Year EFS rate
Time frame: Up to ~84 months
IC vs Control: Five-Year EFS rate
Time frame: Up to ~96 months
ICT vs IC: Two-Year EFS rate
Time frame: Up to ~72 months
ICT vs IC: Three-Year EFS rate
Time frame: Up to ~84 months
ICT vs IC: Five-Year EFS rate
Time frame: Up to ~96 months
ICT vs IC vs Control: Locoregional recurrence-free survival (LRFS) rate
Time frame: Up to ~96 months
ICT vs IC vs Control: Distant Disease-free Survival (DDFS) rate
Time frame: Up to ~96 months
ICT vs IC vs Control: Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL)
Time frame: Up to ~96 months
ICT vs IC vs Control: Change From Baseline in Global Health Status/Physical Functioning Scales
Time frame: Up to ~96 months
ICT vs IC vs Control: Change from Baseline in Swallowing, Speech, and Pain Symptoms
Time frame: Up to ~96 months
ICT vs IC vs Control: Percentage of Participants Experiencing An Adverse Event (AEs)
Time frame: Up to ~96 months
ICT vs IC: Percentage of Participants Discontinuing Study Drug Due to AEs
Time frame: Up to ~48 months
ICT vs IC: OS
Time frame: Up to ~96 months
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 18 Oct 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.
Yue He, M.D. principal investigator
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Toripalimab, Cetuximab and Albumin-Bound Paclitaxel in people with Squamous Cell Carcinoma of Head and Neck, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.
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 14 inclusion and 11 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: opening soon, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Feng Liu, M.D. (18917797783, nuanliu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ICT vs Control: Two-Year Event-free Survival (EFS) rate (time frame: Up to ~72 months). The study lists 2 primary outcomes in all. 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 18 Oct 2024.