Oral Squamous Cell Carcinoma
Conditions
Keywords
Neoadjuvant, Oral squamous cell carcinoma, PD-1 blockade, Camrelizumab, TPF induction chemotherapy
Brief summary
The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.
Detailed description
The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.
Interventions
DRUGCamrelizumab
The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.
DRUGCamrelizumanb plus TPF
The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Hospital of Stomatology, Wuhan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically documented oral squamous cell carcinoma (biopsy required). 2. Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-3M0, T3-4aN0-3M0) with resection option for potential cure, as assessed by a faculty surgeon at Hospital of Stomatology, Wuhan University. 3. Distant metastasis is excluded by chest CT and emission computed tomograph. 4. Adequate organ function as follows: 1) Leukocyte count ≥ 2,000/mm3; 2) Absolute neutrophil count ≥ 1,000/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum albumin ≥30 g/L; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) \< 2.5 × ULN; 8) ALP ≤ 2.5 × ULN; 9) Prothrombin time-international normalized ratio ≤ 1.5; 10) Serum creatinine ≤ 1.5 × ULN; 11) INR/PT≤ 1.5; 12) TSH ≤ ULN. 5. ECOG performance status 0-1. 6. Female patient tested HCG negative in serum or urine within 7 days prior to the start of investigational product. Both patient and partner must agree to use contraception prior to study entry and for the duration of study participation and for up to 120 days after the last dose of PD-1 blockade. 7. Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form.
Exclusion criteria
1. History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment. 2. History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years. 3. Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways. 4. Active autoimmune disease or history of refractory autoimmune disease. 5. Active systemic infection requiring therapy. 6. Patients who are receiving psychotropic drug or alcohol/drug abuse. 7. Subjects with concurrent other active malignancies. 8. HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment. 9. Uncontrollable systemic diseases, including diabetes, hypertension, etc. 10. History of stroke or transient ischemic attack within past 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response. | 8 weeks. | Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Hematoxylin and eosin (H&E)-stained slides of entire tumor and all sampled lymph nodes were scanned and assessed by two independent pathologists. The entire tumor bed and all sampled lymph nodes were examined histologically in patients who had pathological complete response (pCR), which was defined as the absence of viable tumor in all slides. MPR was defined as the presence of 10% or less viable residual tumor in the resected tumor specimens. Pathological partial response (pPR) was defined as presence of more than 10% and less than 50% viable residual tumor and pathological non-response (pNR) was defined as presence of more than 50% viable residual tumor in the resected tumor specimens. Pathologic response was defined as sum of pCR and MPR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Response. | 8 weeks. | Radiographic response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy were evaluated by enhanced computed tomography examinations and defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete Response (CR) was defined as disappearance of all target lesions. Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) was defined as \<20% increase and \<30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) was defined as \>=20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR. |
| Event-free Survival (EFS) Rate on Each Treatment Arm. | 24 months. | EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1. |
| Overall Survival (OS) on Each Treatment Arm. | 24 months. | OS is the time from randomization to death due to any cause. |
| Adverse Events (AEs). | 24 months. | Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Level of Circualting Exosomal PD-L1. | 24 months. | The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA). |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neoadjuvant PD-1 Blockade Alone The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
Camrelizumab: The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery. | 34 |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.
Camrelizumanb plus TPF: The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles. | 34 |
| Total | 68 |
Baseline characteristics
| Characteristic | Neoadjuvant PD-1 Blockade Alone | Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 29 Participants | 57 Participants |
| Age, Continuous | 52.0 years STANDARD_DEVIATION 11.4 | 49.5 years STANDARD_DEVIATION 10 | 50.7 years STANDARD_DEVIATION 10.8 |
| Alcohol use history Current or former | 15 Participants | 18 Participants | 33 Participants |
| Alcohol use history Never | 19 Participants | 16 Participants | 35 Participants |
| Clinical N-stage N0 (No regional lymph node metastasis) better outcomes | 23 Participants | 13 Participants | 36 Participants |
| Clinical N-stage N1 (Metastasis in a single ipsilateral lymph node, 3 cm or less in great est dimension) | 6 Participants | 10 Participants | 16 Participants |
| Clinical N-stage N2 (Lymph node metastasis more than 3 cm but no more than 6 cm in greatest dimension) worse outcomes | 5 Participants | 11 Participants | 16 Participants |
| Clinical T-stage T2 (Tumour more than 2 cm but not more than 4 cm in greatest dimension) better outcomes | 6 Participants | 9 Participants | 15 Participants |
| Clinical T-stage T3 (Tumour more than 4 cm in greatest dimension) | 19 Participants | 18 Participants | 37 Participants |
| Clinical T-stage T4a (Tumour invades through cortical bone, maxillary sinus) worse outcomes | 9 Participants | 7 Participants | 16 Participants |
| PD-L1 combined positive score 1-19 (Considered as positive PD-L1 expression) | 12 Participants | 18 Participants | 30 Participants |
| PD-L1 combined positive score <1 (Considered as negative PD-L1 expression) worse outcomes | 16 Participants | 13 Participants | 29 Participants |
| PD-L1 combined positive score >=20 (Considered as positive PD-L1 expression) better outcomes | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 34 Participants | 68 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 34 participants | 34 participants | 68 participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 28 Participants | 31 Participants | 59 Participants |
| Smoking history Current or former | 24 Participants | 22 Participants | 46 Participants |
| Smoking history Never | 10 Participants | 12 Participants | 22 Participants |
| Tumor site Buccal mucosa | 7 Participants | 9 Participants | 16 Participants |
| Tumor site Floor of mouth | 4 Participants | 4 Participants | 8 Participants |
| Tumor site Gingiva | 5 Participants | 3 Participants | 8 Participants |
| Tumor site Oral tongue | 18 Participants | 18 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 1 / 34 |
| other Total, other adverse events | 34 / 34 | 34 / 34 |
| serious Total, serious adverse events | 2 / 34 | 11 / 34 |
Outcome results
Primary
Pathologic Response.
Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Hematoxylin and eosin (H&E)-stained slides of entire tumor and all sampled lymph nodes were scanned and assessed by two independent pathologists. The entire tumor bed and all sampled lymph nodes were examined histologically in patients who had pathological complete response (pCR), which was defined as the absence of viable tumor in all slides. MPR was defined as the presence of 10% or less viable residual tumor in the resected tumor specimens. Pathological partial response (pPR) was defined as presence of more than 10% and less than 50% viable residual tumor and pathological non-response (pNR) was defined as presence of more than 50% viable residual tumor in the resected tumor specimens. Pathologic response was defined as sum of pCR and MPR.
Time frame: 8 weeks.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neoadjuvant PD-1 Blockade Alone | Pathologic Response. | Number of participants who had no response | 25 Participants |
| Neoadjuvant PD-1 Blockade Alone | Pathologic Response. | Number of participants who had partial response | 4 Participants |
| Neoadjuvant PD-1 Blockade Alone | Pathologic Response. | Number of Participants Pathologic response (pCR+MPR) | 5 Participants |
| Neoadjuvant PD-1 Blockade Alone | Pathologic Response. | Non-evaluable | 0 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Pathologic Response. | Non-evaluable | 2 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Pathologic Response. | Number of participants who had no response | 2 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Pathologic Response. | Number of Participants Pathologic response (pCR+MPR) | 26 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Pathologic Response. | Number of participants who had partial response | 4 Participants |
Secondary
Adverse Events (AEs).
Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions.
Time frame: 24 months.
Secondary
Event-free Survival (EFS) Rate on Each Treatment Arm.
EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1.
Time frame: 24 months.
Secondary
Overall Survival (OS) on Each Treatment Arm.
OS is the time from randomization to death due to any cause.
Time frame: 24 months.
Secondary
Radiographic Response.
Radiographic response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy were evaluated by enhanced computed tomography examinations and defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete Response (CR) was defined as disappearance of all target lesions. Partial Response (PR) was defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) was defined as \<20% increase and \<30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) was defined as \>=20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.
Time frame: 8 weeks.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neoadjuvant PD-1 Blockade Alone | Radiographic Response. | PR (Partial response) | 3 Participants |
| Neoadjuvant PD-1 Blockade Alone | Radiographic Response. | PD (Progressive disease) | 11 Participants |
| Neoadjuvant PD-1 Blockade Alone | Radiographic Response. | Non-evaluable | 0 Participants |
| Neoadjuvant PD-1 Blockade Alone | Radiographic Response. | SD (Stable disease) | 20 Participants |
| Neoadjuvant PD-1 Blockade Alone | Radiographic Response. | CR (Complete response) | 0 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Radiographic Response. | PD (Progressive disease) | 1 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Radiographic Response. | CR (Complete response) | 0 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Radiographic Response. | PR (Partial response) | 16 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Radiographic Response. | SD (Stable disease) | 14 Participants |
| Neoadjuvant PD-1 Blockade Plus TPF Induction Chemotherapy | Radiographic Response. | Non-evaluable | 3 Participants |
Other Pre-specified
Changes in the Level of Circualting Exosomal PD-L1.
The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA).
Time frame: 24 months.