Head and Neck CancersPhase 2NCT06894459
A Prospective, Multicenter, Multicohort Phase II Study: Evaluating the Efficacy and Safety of Preoperative Neoadjuvant Treatment With a PD-1 Inhibitor in Combination With Chemotherapy in Locally Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma
A Phase 2 study testing Pembrolizumab, Cisplatin and Nab-paclitaxel in people with Head and Neck Cancers, run by Beijing Tongren Hospital.
Trial summary
Head and neck squamous cell carcinoma (HNSCC) refers to a series of tumors that occur in the head and neck region, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid gland, and salivary glands. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancers
- What is being tested?
- Pembrolizumab, Cisplatin and Nab-paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- 8 May 2025to 1 Dec 2028
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma who have been definitively diagnosed by histology and/or cytology, and whose TN staging meets: T1-4a, N0-3.
- No prior treatment received.
- Cisplatin-tolerant.
- Age ≥18 years.
- ECOG performance status of 0-1.
- Measurable disease as defined by RECIST v1.1.
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- Normal organ function.
- Women and men of reproductive potential must agree to use appropriate contraceptive methods throughout the study period and for 180 days after the last study treatment.
- Male participants must not donate sperm during the entire study period and for 180 days after the last study treatment.
Who cannot join
- T stage is T4b.
- Presence of distant metastasis.
- Received live vaccines within 30 days prior to enrollment.
- Diagnosed with an immunodeficiency or received systemic corticosteroid treatment or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- Have radiologically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis.
- Have not fully recovered from surgery or from toxicities or complications due to interventions before starting the study.
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- Have a history of allogeneic tissue/solid organ transplantation.
- Have had a severe hypersensitivity reaction (≥Grade 3) to PD-1 inhibitors, chemotherapy, or any of their excipients, or radiotherapy.
- Have an active autoimmune disease that has required systemic therapy within the past 2 years.
- Have a history of (non-infectious) pneumonitis that required treatment with corticosteroids.
- Have a history of infection with the Human Immunodeficiency Virus (HIV).
- Have a medical history that could confound study results or interfere with the participant during the study period.
- Have a known history of psychiatric disorders or substance abuse.
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
Head and neck squamous cell carcinoma (HNSCC) refers to a series of tumors that occur in the head and neck region, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid gland, and salivary glands. Malignant tumors of the head and neck account for approximately 19.9% to 30.2% of all tumors in the body, ranking sixth in incidence among all malignant tumors, with over 90% being squamous cell carcinoma in terms of pathological type. The treatment of head and neck squamous cell carcinoma is primarily surgical. Early-stage cases can achieve a cure through simple surgical resection or radiotherapy. For locally advanced and late-stage cases, a combination of surgery with radiotherapy or chemotherapy can yield satisfactory therapeutic effects. However, most patients with head and neck tumors present at a locally advanced (Stage III to IVB) or late stage, possibly having lost the opportunity for surgery and can only opt for a comprehensive treatment mainly based on radiochemotherapy. Current data show that with standard treatment, the 5-year survival rates for patients with early-stage, locally advanced, and metastatic head and neck squamous cell carcinoma are 80%, 50%, and 25%, respectively. Fifty to sixty percent of newly diagnosed subjects cannot be cured and experience recurrence or metastasis within 3 years. For patients with recurrent or metastatic disease after first-line treatment failure, the median survival time with chemotherapy is only 6 to 9 months, with a 1-year survival rate of 5% to 33% and a 5-year survival rate of merely 3.6%. Laryngeal cancer and hypopharyngeal cancer hold unique significance among head and neck tumors because they not only threaten patients' lives but can also significantly affect their quality of life, particularly the preservation of laryngeal function. Laryngeal function includes voice production, swallowing, and breathing, and the loss of these functions can lead to a severe decline in quality of life. Traditionally, surgical resection has been the main treatment for these cancers, but total laryngectomy can result in permanent voice loss and significant psychological and social impacts. Therefore, how to effectively control the tumor while preserving laryngeal function has become an important goal of treatment.
PD-L1 is a key negative regulator of self-reactive T cells and plays a role in maintaining peripheral immune tolerance and suppressing autoimmunity in various ways, leading to T cell exhaustion and dysfunction, and allowing tumor cells to evade immune surveillance. PD-1/PD-L1 monoclonal antibodies restore the function of tumor-specific T cells by blocking the binding of PD-1 to PD-L1, thereby enhancing antitumor immunity and are now used to treat a variety of tumors. The efficacy of PD-1 inhibitors as neoadjuvant therapy in head and neck squamous cell carcinoma is not yet clear. However, given the good therapeutic effects of immunotherapy in head and neck squamous cell carcinoma, induction therapy with PD-1 inhibitors is considered to have promising clinical application prospects.
In summary, we hypothesize that compared with the traditional TPF (docetaxel, cisplatin, and fluorouracil) neoadjuvant chemotherapy regimen, a PD-1 inhibitor combined with chemotherapy regimen may be safer and more effective and easier to apply in clinical practice. At present, there are no reports of studies on the use of PD-1 inhibitors combined with chemotherapy regimens for locally advanced, resectable head and neck squamous cell carcinoma patients, either domestically or internationally. We plan to investigate the efficacy and safety of neoadjuvant treatment with PD-1 inhibitors combined with chemotherapy for resectable head and neck squamous cell carcinoma patients in China, to provide a basis for future neoadjuvant treatment regimens.
- Conditions
- Head and Neck Cancers
- Being tested
- Pembrolizumab, Cisplatin, Nab-paclitaxel
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab 200mg, IV, 3 cycles
CisplatinDrug
cisplatin 75mg/m2, IV, 3 cycles
Nab-paclitaxelDrug
Nab-paclitaxel 260mg, IV, 3 cycles
| Study group | Role | What they receive |
|---|---|---|
| pCR group | Experimental | Patients with a pathological complete response (pCR) post-surgery receive adjuvant radiotherapy (50-56 Gy, 2.0 Gy/fraction). Receives: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Nab-paclitaxel |
| Non-pCR but without high-risk factors group | Experimental | Patients with non-pCR but without high-risk factors receive a combination of radiotherapy (56-60 Gy, 2.0 Gy/fraction) and cisplatin chemotherapy post-surgery. Receives: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Nab-paclitaxel |
| Non-pCR and high-risk factors group | Experimental | Patients with non-pCR and high-risk factors receive intensified radiotherapy (66-70 Gy, 2.0 Gy/fraction) along with cisplatin chemotherapy post-surgery. Receives: Drug: Pembrolizumab; Drug: Cisplatin; Drug: Nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year progression-free survival rate (2y-PFS rate)
To evaluate the 2y-PFS rate of neoadjuvant PD-1 inhibitors combined with chemotherapy in 3 arms; PFS was defined as the time from patient enrollment to the occurrence of the following events (local progression/recurrence or distant metastasis (including neoadjuvant stage) assessed by imaging or biopsy, death from any cause)
Measured: 2 years
Secondary outcomes (5)
Pathological complete response rate (pCR rate)
To evaluate the pCR rate of neoadjuvant PD-1 inhibitors combined with chemotherapy in 3 arms; pCR was defined as the absence of residual invasive squamous cell carcinoma cells in the resected primary tumor specimen and lymph nodes
Measured: 3 months
Objective response rate (ORR)
To evaluate the ORR of neoadjuvant therapy with PD-1 inhibitors plus chemotherapy in 3 Arms; ORR is defined as The proportion of patients whose tumor volume shrinks to a pre-specified value and can be maintained for a certain period of time. It includes the proportion of patients with complete remission (CR) and partial remission (PR) to the total number of evaluable cases.
Measured: 6 months
2-year overall survival rate (2y-OS rate)
To evaluate the 2y-OS rate of neoadjuvant PD-1 inhibitors plus chemotherapy in 3 Arms; OS was defined as the time from randomization until death from any cause.
Measured: 2 years
Progression-Free Survival(PFS)
To evaluate the PFS of neoadjuvant PD-1 inhibitors plus chemotherapy in 3 arms in the overall population; PFS is defined as the length of time during and after treatment that a patient lives with a disease that does not get worse.
Measured: 2 years
Incidence of Treatment-Emergent Adverse Events (TRAEs) of pembrolizumab combined with chemotherapy in neoadjuvant therapy
TRAEs include 5 levels, base on Common Terminology Criteria for Adverse Events (CTCAE) is widely accepted as the standard classification and severity grading scale for adverse events in cancer therapy, clinical trials and other oncology settings.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start8 May 2025 (estimated)
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2028 (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 CancersStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tongren Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06894459
- Sponsor's protocol ID
- TRENT-003
- Status last verified
- Oct 2024
- First submitted
- 19 Mar 2025
- Last updated
- 30 Apr 2025
- 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 30 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Multicohort Phase II Study: Evaluating the Efficacy and Safety of Preoperative Neoadjuvant Treatment With a PD-1 Inhibitor in Combination With Chemotherapy in Locally Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06894459
- Acronym / sponsor ID
- TRENT-003
- Conditions
- Head and Neck Cancers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Beijing Tongren HospitalUniversity, hospital or other
- Study start
- 8 May 2025 (estimated)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 25 Mar 2025 (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.
Head and neck squamous cell carcinoma (HNSCC) refers to a series of tumors that occur in the head and neck region, including the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid gland, and salivary glands. Malignant tumors of the head and neck account for approximately 19.9% to 30.2% of all tumors in the body, ranking sixth in incidence among all malignant tumors, with over 90% being squamous cell carcinoma in terms of pathological type. The treatment of head and neck squamous cell carcinoma is primarily surgical. Early-stage cases can achieve a cure through simple surgical resection or radiotherapy. For locally advanced and late-stage cases, a combination of surgery with radiotherapy or chemotherapy can yield satisfactory therapeutic effects. However, most patients with head and neck tumors present at a locally advanced (Stage III to IVB) or late stage, possibly having lost the opportunity for surgery and can only opt for a comprehensive treatment mainly based on radiochemotherapy. Current data show that with standard treatment, the 5-year survival rates for patients with early-stage, locally advanced, and metastatic head and neck squamous cell carcinoma are 80%, 50%, and 25%, respectively. Fifty to sixty percent of newly diagnosed subjects cannot be cured and experience recurrence or metastasis within 3 years. For patients with recurrent or metastatic disease after first-line treatment failure, the median survival time with chemotherapy is only 6 to 9 months, with a 1-year survival rate of 5% to 33% and a 5-year survival rate of merely 3.6%. Laryngeal cancer and hypopharyngeal cancer hold unique significance among head and neck tumors because they not only threaten patients' lives but can also significantly affect their quality of life, particularly the preservation of laryngeal function. Laryngeal function includes voice production, swallowing, and breathing, and the loss of these functions can lead to a severe decline in quality of life. Traditionally, surgical resection has been the main treatment for these cancers, but total laryngectomy can result in permanent voice loss and significant psychological and social impacts. Therefore, how to effectively control the tumor while preserving laryngeal function has become an important goal of treatment.
PD-L1 is a key negative regulator of self-reactive T cells and plays a role in maintaining peripheral immune tolerance and suppressing autoimmunity in various ways, leading to T cell exhaustion and dysfunction, and allowing tumor cells to evade immune surveillance. PD-1/PD-L1 monoclonal antibodies restore the function of tumor-specific T cells by blocking the binding of PD-1 to PD-L1, thereby enhancing antitumor immunity and are now used to treat a variety of tumors. The efficacy of PD-1 inhibitors as neoadjuvant therapy in head and neck squamous cell carcinoma is not yet clear. However, given the good therapeutic effects of immunotherapy in head and neck squamous cell carcinoma, induction therapy with PD-1 inhibitors is considered to have promising clinical application prospects.
In summary, we hypothesize that compared with the traditional TPF (docetaxel, cisplatin, and fluorouracil) neoadjuvant chemotherapy regimen, a PD-1 inhibitor combined with chemotherapy regimen may be safer and more effective and easier to apply in clinical practice. At present, there are no reports of studies on the use of PD-1 inhibitors combined with chemotherapy regimens for locally advanced, resectable head and neck squamous cell carcinoma patients, either domestically or internationally. We plan to investigate the efficacy and safety of neoadjuvant treatment with PD-1 inhibitors combined with chemotherapy for resectable head and neck squamous cell carcinoma patients in China, to provide a basis for future neoadjuvant treatment regimens.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| pCR group | Experimental | Drug: Pembrolizumab, Drug: Cisplatin, Drug: Nab-paclitaxelPatients with a pathological complete response (pCR) post-surgery receive adjuvant radiotherapy (50-56 Gy, 2.0 Gy/fraction). |
| Non-pCR but without high-risk factors group | Experimental | Drug: Pembrolizumab, Drug: Cisplatin, Drug: Nab-paclitaxelPatients with non-pCR but without high-risk factors receive a combination of radiotherapy (56-60 Gy, 2.0 Gy/fraction) and cisplatin chemotherapy post-surgery. |
| Non-pCR and high-risk factors group | Experimental | Drug: Pembrolizumab, Drug: Cisplatin, Drug: Nab-paclitaxelPatients with non-pCR and high-risk factors receive intensified radiotherapy (66-70 Gy, 2.0 Gy/fraction) along with cisplatin chemotherapy post-surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with locally advanced laryngeal and hypopharyngeal squamous cell carcinoma who have been definitively diagnosed by histology and/or cytology, and whose TN staging meets: T1-4a, N0-3.
- No prior treatment received.
- Cisplatin-tolerant.
- Age ≥18 years.
- ECOG performance status of 0-1.
Key exclusion criteria (13 listed)
- T stage is T4b.
- Presence of distant metastasis.
- Received live vaccines within 30 days prior to enrollment.
- Diagnosed with an immunodeficiency or received systemic corticosteroid treatment or any other form of immunosuppressive therapy within 7 days prior to enrollment.
- Have radiologically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis.
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 |
|---|---|---|
| PembrolizumabPembrolizumab 200mg, IV, 3 cycles | Drug | Non-pCR and high-risk factors group, Non-pCR but without high-risk factors group, pCR group |
| Cisplatincisplatin 75mg/m2, IV, 3 cycles | Drug | Non-pCR and high-risk factors group, Non-pCR but without high-risk factors group, pCR group |
| Nab-paclitaxelNab-paclitaxel 260mg, IV, 3 cycles | Drug | Non-pCR and high-risk factors group, Non-pCR but without high-risk factors group, pCR group |
Primary outcome
2-year progression-free survival rate (2y-PFS rate)
Time frame: 2 years
To evaluate the 2y-PFS rate of neoadjuvant PD-1 inhibitors combined with chemotherapy in 3 arms; PFS was defined as the time from patient enrollment to the occurrence of the following events (local progression/recurrence or distant metastasis (including neoadjuvant stage) assessed by imaging or biopsy, death from any cause)
5 secondary outcomes
Pathological complete response rate (pCR rate)
Time frame: 3 months
Objective response rate (ORR)
Time frame: 6 months
2-year overall survival rate (2y-OS rate)
Time frame: 2 years
Progression-Free Survival(PFS)
Time frame: 2 years
Incidence of Treatment-Emergent Adverse Events (TRAEs) of pembrolizumab combined with chemotherapy in neoadjuvant therapy
Time frame: 3 years
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 2025.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Cisplatin and Nab-paclitaxel in people with Head and Neck Cancers, run by Beijing Tongren Hospital.
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 9 inclusion and 13 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 30 Apr 2025. 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 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 Xiaohong Chen (08658269106, trchxh@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year progression-free survival rate (2y-PFS rate) (time frame: 2 years). 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 2025.