Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Gemcitabine

Rituximab

Cisplatin

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

* Drug:Rituximab
* Drug:Cisplatin
* Drug:Gemcitabine

Head and neck squamous cell carcinoma (HNSCC) is an important disease with the incidence of 6th all over the world. In Taiwan it is the fifth of male cancer mortality. Most of the patients were middle age and the impact for economy and society was incredible. For recurrent or metastatic HNSCC, the average life span was around 4-6 months. Most patients just can receive chemotherapy. However the chemotherapy can't have any survival benefit. Recently a study showed the Cetuximab plus chemotherapy with cisplatin and 5-fluorouracil had survival benefit in the recurrent or metastatic HNSCC. However in Taiwan, the cetuximab can't be given by health insurance for the patients of the situation.

A lot of investigations recently showed the B lymphocytes got involvements in the squamous cell carcinoma carcinogenesis and tumor progression. In addition the B cell will influence the tumor associated macrophages and myeloid derived suppressor cells. Those immune cells could decrease the affect of chemotherapy and radiotherapy. Thus the B cell depletion has the possibility to develop a new treatment policy. Therefore investigators create a pilot clinical trial using Rituximab plus chemotherapy with cisplatin and gemcitabine for recurrent or metastatic HNSCC.

Rituximab Plus Chemotherapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

A Phase I Pilot Study of B Cell Depletion With Rituximab Following by Chemotherapy With Cisplatin Plus Gemcitabine for Recurrent Unresectable or Metastatic Head and Neck Cancer Squamous Cell Carcinoma Patients.

Unexpected adverse event. An AE that is not listed in the drug's current labeling, or An AE that is more severe or more specific than indicated in the labeling.

CT scan according to the RECIST 1.1 criteria.

The time from the study registration date to the first day of disease progression at any site or of death by any cause.

China Medical University Hospital

attending physician

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunomodulating Agents

Immunoglobulins

Step 1：neoadjuvant anti-PD-1 antibody and TP chemotherapy every 3 weeks 2 cycles

Step 2： SBRT with GTV expanded 3mm , 24Gy/3F, every other day within one week after the immunochemotherapy

Step 3：Subsequent surgery and adjuvant treatments.

Radical surgery will be performed within 4-6 weeks after the second cycle of immunochemotherapy，no matter the situation of the tumor regresses.

Patients with pathological MPR/CR were treated with PD-1 antibody every two weeks up to 6 cycles after surgery with no adjuvant chemoradiotherapy. Those not achieved MPR/CR will receive adjuvant radiotherapy or chemoradiotherapy according to NCCN guidelines.

Step 1：neoadjuvant anti-PD-1 antibody and TP chemotherapy every 3 weeks 2 cycles

Step 2：Subsequent surgery and adjuvant treatments.

Radical surgery will be performed within 4-6 weeks after the second cycle of immunochemotherapy，no matter the situation of the tumor regresses.

Patients with pathological MPR/CR were treated with PD-1 antibody every two weeks up to 6 cycles after surgery without adjuvant chemoradiotherapy. Those not achieved MPR/CR will receive adjuvant radiotherapy or chemoradiotherapy according to NCCN guidelines.

Step 1：neoadjuvant anti-PD-1 antibody and TP chemotherapy combined with cetuximab every 3 weeks for 2 cycles

step2: Subsequent surgery and adjuvant treatments.

Radical surgery will be performed within 4-6 weeks after the second cycle of immunochemotherapy，no matter the situation of the tumor regresses.

Patients with pathological MPR/CR were treated with PD-1 antibody and cetuximab every two weeks up to 6 cycles after surgery without adjuvant chemoradiotherapy. Those not achieved MPR/CR will receive adjuvant radiotherapy or chemoradiotherapy according to NCCN guidelines.

SBRT radiotherapy，followed with PD-1 monoclonal antibody and TP chemotherapy

SBRT+immunochemotherpy

PD-1 monoclonal antibody and TP chemotheapy

Immunochemotherapy

PD-1 monoclonal antibody and TP chemotheapy combined with cetuximab

cetuximab+immunochemotharpy

Feng Jiang, MD

feng Jiang, MD

The response rate of HNSCC to immune checkpoint blockade was not satisfied. Improving the mPR rate of neoadjuvant immunotherapy through the combination with other treatment methods is an important way to further improve the prognosis of such patients. This study aims to explore the efficacy and safety of PD-1 monoclonal antibody with neoadjvant SBRT and chemotherapy. The triple mode not only can Increase the effectiveness of neoadjuvant therapy，meanwhile，the in situ tumor vaccine inoculation effect generated by enhancing the release of specific antigens after tumor radiotherapy with PD-1 monoclonal antibody achieves a sustained anti-tumor immune effect throughout the body， reducing postoperative adjuvant radiotherapy and chemotherapy. The triple mode has important exploratory value in achieving high quality and long-term survival for patients, and may provides a more efficient mode for locally advanced HNSCC.

locally advanced HNSCC patients would receive PD-1 antibody and chemotherapy with or without SBRT covering GTV of primary disease and metastatic nodes , followed by surgery. pathological response was measured .Neoadjuvant PD-1 antibody and chemotherapy with certuxmab was also tested

Neoadjuvant SBRT in Localized Advanced HNSCC

Neoadjuvant Stereotactic Body Radiotherapy（SBRT）Combined With Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Jiang Feng

principal investigator

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Prostatic Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Carcinoma, Transitional Cell

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

Anti-Infective Agents

Analgesics

Aldesleukin

Nivolumab

Interleukin-2

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Single dose of NeoTCR-P1 plus nivolumab 480mg IV every four weeks for up to 6 doses.

Single dose of NeoTCR-P1 plus IL-2 500,000 IU/m2 SC twice daily (BID) for 7 days.

The investigational agent in this protocol is NeoTCR P1, an autologous adoptive T cell therapy (ACT) for patients with solid cancer. NeoTCR P1 is composed of apheresis derived CD8 and CD4 T cells that are precision genome engineered to express one autologous TCR of native sequence that targets a neoepitope (neoE) presented by human leukocyte antigen (HLA) receptors exclusively on the surface of that patient's tumor cells and not on other cells in the body.

NeoTCR-P1 adoptive cell therapy

Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody

nivolumab

IL-2 is a biologic response modifier. It is a type of protein called a cytokine.

IL-2

This is a first in human, single arm, open label, Phase 1a/1b study to determine the safety, feasibility, and efficacy of a single dose of NeoTCR-P1 T cells in participants with solid tumors.

A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors

A Phase 1a/1b, Open-label First-in-human Study of the Safety, Tolerability and Feasibility of Gene-edited Autologous NeoTCR-T Cells (NeoTCR-P1) Administered as a Single Agent or in Combination With Anti-PD-1 to Patients With Locally Advanced or Metastatic Solid Tumors

Dose limiting toxicity (DLT) is defined as protocol-defined adverse events that occur within 28 days following infusion of Neo-TCR-P1 administered as a single agent without or with IL-2, or in combination with nivolumab.

Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Cytokine release syndrome (CRS) and neurotoxicity associated with NeoTCR-P1 will be graded according to ASBMT consensus grading.

The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.

Percent of screened patients that enroll on study and receive NeoTCR-P1

ORR will be defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1, as determined by the investigator

Duration of response, defined as time from the first occurrence of a documented objective response to the time of relapse or death from any cause

PFS is defined from date of administration of NeoTCR-P1 cell infusion to the date of disease progression per the RECIST v1.1 or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis data cut-off date will be censored at their last evaluable disease assessment date

OS will be measured from the date of administration of NeoTCR-P1 to the date of death. Subjects who have not died by the analysis data cut-off date will be censored at their last date of contact.

PACT Pharma, Inc.

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

SCT200+SCT-I10A was given to patients who had failed previous platinum-based therapy. Among them, SCT200 was administered as 6 mg/kg/QW for 12 weeks and 8 mg/kg/Q2W maintenance by intravenous infusion; SCT-I10A was 200 mg/Q3W by intravenous infusion for no more than 2 years. Every 6 weeks is a treatment cycle. After the first dose, tumor assessment was performed every 6 weeks until the occurrence of PD, initiation of new antitumor therapy, withdrawal of informed consent, death, or loss of visit

SCT200+SCT-I10A was given to patients who had failed previous platinum-based and immune checkpoint inhibitor therapy. Among them, SCT200 was administered as 6 mg/kg/QW for 12 weeks and 8 mg/kg/Q2W maintenance by intravenous infusion; SCT-I10A was 200 mg/Q3W by intravenous infusion for no more than 2 years. Every 6 weeks is a treatment cycle. After the first dose, tumor assessment was performed every 6 weeks until the occurrence of PD, initiation of new antitumor therapy, withdrawal of informed

SCT200+paclitaxel/docetaxel was given to patients who had failed previous platinum-based and immune checkpoint inhibitor therapy. Among them, SCT200 was administered as 6 mg/kg/QW for 12 weeks and 8 mg/kg/Q2W maintenance by intravenous infusion; paclitaxel was 80mg/m\^2/QW by intravenous infusion; docetaxel was 75mg/m\^2/Q3W. Every 6 weeks is a treatment cycle. After the first dose, tumor assessment was performed every 6 weeks until the occurrence of PD, initiation of new antitumor therapy, withdrawal of informed

SCT200+SCT-I10A was given to patients who have not received prior systemic chemotherapy. Among them, SCT200 was administered as 6 mg/kg/QW for 12 weeks and 8 mg/kg/Q2W maintenance by intravenous infusion; SCT-I10A was 200 mg/Q3W by intravenous infusion for no more than 2 years. Every 6 weeks is a treatment cycle. After the first dose, tumor assessment was performed every 6 weeks until the occurrence of PD, initiation of new antitumor therapy, withdrawal of informed

SCT-I10A

SCT200

paclitaxel

docetaxel

Fuqiang Chen

Chaodan Tan

Ye Guo, Ph.D

The study is to explore the efficacy and safety of SCT200 with SCT-I10A or SCT200 combined with paclitaxel/docetaxel in the treatment of recurrent/metastatic head and neck squamous cell carcinoma.

This multicenter, open phase Ib study focused on evaluating the objective response response rates of SCT200 in combination with SCT-I10A or SCT200 in combination with paclitaxel/docetaxel in patients with recurrent/metastatic head and neck squamous cell carcinoma who had previously received different treatments.

SCT200 in Combination With SCT-I10A/Paclitaxel/Docetaxel in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

A Multicenter, Open Phase Ib Study to Evaluate the Efficacy and Safety of SCT-I10A in Combination With SCT200 or SCT200 in Combination With Paclitaxel/Docetaxel in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0. An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product.

Serum anti-SCT200 antibody and anti-SCT-I10A antibody levels before and after administration

ORR is defined as the proportion of subjects with complete response (CR) or partial response (PR) confirmed by the overall best response rate (assessed according to RECIST version 1.1).

DCR is defined as the proportion of subjects who achieve best overall response of complete response (CR), partial response (PR) or stable disease (SD) according to RECIST version 1.1

DOR is defined as the time from first response to first disease progression or death

PFS is defined as the time between the date of first dose and the date of first documented disease progression (as assessed by RECIST version 1.1) or death from any cause.

OS is defined as the time from the date of first drug administration to death from any cause.

For cohort1、2-1 and 3, evaluating correlation of PD-L1 expression level with efficacy and prognosis

Sinocelltech Ltd.

Nedaplatin

Nedplatin combined with intensive radiotherapy group

Cisplatin was combined with the IMRT group

Nedaplatin is a second-generation platinum-like derivative, which is a cell cycle non-specific drug, with a mechanism of action and efficacy similar to cisplatin, and a wide anti-cancer spectrum

Cisplatin, aka cis-dichlorodiamineplatin, is a platinum-containing anticancer drug

Feng Jin, Bachelor

Weili Wu, Master

Weili Wu, master

Yuanyuan Li, master

Jinhua Long, master

Xiuyun Gong, bachelor

Xiaoxiao Chen, bachelor

Mang Zhang, master

This study was designed as a prospective, multicenter and randomized clinical study of radiotherapy combined with Nedaplatin contrast and cisplatin for local advanced head and neck squamous SCC, aiming to explore the efficacy, safety and long-term efficacy of this trial and control groups and provide some evidence for the selection of clinical treatment options.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy accounting for more than 90% of head and neck tumors and over 60% of patients with mid-to late stage (-b) stage at diagnosis.For patients with moderate and advanced head and neck squamous carcinoma, concurrent chemoradiotherapy and chemotherapy is recommended for category 1 and the preferred drug is cisplatin.The application of simultaneous chemoradiotherapy can significantly improve the overall survival rate of patients with locally advanced head and neck squamous carcinoma, and effectively reduce their local recurrence rate and distant metastasis rate.However, the application of cisplatin aggravates the toxic and side reactions, such as nausea and vomiting, radioactive oral mucosal response, nephrotoxicity and ear toxicity.Although the clinical benefit of synchronous chemochemotherapy of locally advanced head and neck squamous carcinoma with cisplatin as chemotherapy is considerable, due to its obvious toxic and side reaction, some patients can not tolerate, cannot complete the whole course of treatment and quality of life, resulting in a substantial reduction in the treatment effect.Therefore, in synchronous chemoradiotherapy of locally advanced head and NSCC, there is an urgent need to find an efficient, hypotoxic, novel chemotherapeutic agent to address this problem.

Nedaplatin is the second generation platinum derivative, for cell cycle nonspecific drugs, mechanism and efficacy similar to cisplatin, anticancer spectrum, and cisplatin without drug resistance, cisplatin resistance still has a good effect, its gastrointestinal reaction and nephrotoxicity is significantly reduced, main dose-limiting toxicity, grade marrow suppression, clinical application without hydration, patients good tolerance and convenient to use, can significantly improve the quality of life of patients.A number of foreign studies have found that nedaplatin combination chemotherapy is effective in esophageal cancer, non-small cell lung cancer and cervical cancer, patients are tolerated, and the digestive tract response is significantly reduced, which helps to ensure the integrity of the course of treatment.Wang Zhennan and other studies reported that nedaplatin can improve the radiosensitivity of NPC CNE-2 cells and show dose-dependent inhibition of tumor cells.Koizumi et al also found that nedaplatin with radiotherapy could effective sensitization.In addition, the results of a phase III randomized controlled trial from the Cancer Center of Sun Yat-sen University, which showed that the overall efficiency of nedaplatin combined radiotherapy for local advanced NPC and 2-year progression-free survival rate were no less than cisplatin (88.7%vs89.7%), and compared with the cisplatin group, gastrointestinal loss, nausea, vomiting and weight loss quality score were significantly improved.

Clinical Study of Radiotherapy Combined With Nedaplatin Contrast and Cisplatin for the Treatment of Locally Advanced Head and Neck Squamous Carcinoma

Prospective, Multicentric, Randomized Clinical Study of Radiotherapy Combined With Nedaplatin Contrast and Cisplatin for the Treatment of Locally Advanced Head and Neck Squamous Carcinoma

Overall survival was assessed at 5 years after the end of chemoradiotherapy during the same period

Progression-free survival rate was assessed at 5 years after the end of chemoradiotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rituximab Plus Chemotherapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma	NCT04361409	Head and Neck S...	Rituximab Cisplatin Gemcitabine	20 Years - 65 Years	China Medical University Hospital
Neoadjuvant SBRT in Localized Advanced HNSCC	NCT06306846	Head and Neck S...	SBRT+immunochem... Immunochemother... cetuximab+immun...	18 Years - 70 Years	Zhejiang Cancer Hospital
Neoadjuvant SBRT in Localized Advanced HNSCC	NCT06306846	Head and Neck S...	SBRT+immunochem... Immunochemother... cetuximab+immun...	18 Years - 70 Years	Zhejiang Cancer Hospital
A Study of Gene Edited Autologous Neoantigen Targeted TCR T Cells With or Without Anti-PD-1 in Patients With Solid Tumors	NCT03970382	Solid Tumor	NeoTCR-P1 adopt... nivolumab IL-2	18 Years -	PACT Pharma, Inc.
SCT200 in Combination With SCT-I10A/Paclitaxel/Docetaxel in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma	NCT05552807	Head and Neck S...	SCT-I10A SCT200 paclitaxel docetaxel	18 Years -	Sinocelltech Ltd.
Clinical Study of Radiotherapy Combined With Nedaplatin Contrast and Cisplatin for the Treatment of Locally Advanced Head and Neck Squamous Carcinoma	NCT05039606	Head and Neck S...	Nedaplatin Cisplatin	18 Years - 70 Years	Guiyang Medical University
Neoadjuvant SBRT in Localized Advanced HNSCC	NCT06306846	Head and Neck S...	SBRT+immunochem... Immunochemother... cetuximab+immun...	18 Years - 70 Years	Zhejiang Cancer Hospital

Spots Global Cancer Trial Database for head and neck squamous carcinoma