PD-1 Inhibitor Based Induction Chemotherapy Followed by De-escalation Protocols in OPSCC

Oropharyngeal Cancer Clinical Trial

Official title:

Selective De-escalation of Radiotherapy Density Based on Response to Induction Chemotherapy With PD-1 Inhibitor Toripalimab, Docetaxel, Cisplatin, and Capecitabine in Locally Advanced Oropharyngeal Carcinoma: A Prospective Phase II Trial (DEDICATE-1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06156891
• Other study ID #: 2022145-1
• Status: Recruiting
• Phase: Phase 2
• Start date: June 29, 2022
• Est. completion date: July 30, 2025

Study information

• Verified date: November 2023
• Source: Fudan University
• Contact: Xiaoshen Wang, MD, Ph.D
• Phone: 18917785187
• Email: xiaoshen.wang[@]fdeent.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

More and more studies have shown that the efficacy and prognosis of HPV （Human papillomavirus）-positive oropharyngeal cancer (OPC) patients are better than those of others. However, in the NCCN (National Comprehensive Cancer Network) Oncology Clinical Guidelines for OPC treatment, each group of p16+ is consistent with the corresponding group of p16-, which indicates that the treatment of OPC is basically the same regardless of whether it is related to HPV. Several studies attempted to reduce the toxicities of treatment of HPV related OPC through reduced-dose radiation and showed promising results, and all of the studies have shown that induction chemotherapy is a good way to screen followed treatment. Those who are effective in induction chemotherapy are usually more sensitive to radiation therapy, and reducing the intensity of subsequent treatment will not affect the survival outcome of patients. Immune checkpoint inhibitors (ICIs) have proved to improve outcomes of head and neck cancers. However, In KEYMAT-048, a Phase III controlled trial of relapsed/metastatic head and neck squamous cell carcinoma, ICIs showed an overall survival advantage, but the survival advantage was independent of HPV status. Therefore, patients with HPV-negative OPC still have a good response to ICIs. So we added anti-PD-1 antibody Toripalimab to induction chemotherapy in order to achieve better response rates to receive de-escalation chemoradiotherapy followed regardless of whether it is related to HPV.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 30, 2025
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Histological diagnosis of squamous cell carcinoma of oropharynx; IHC p16 positive or PCR HPV16 positive; IHC p16 negative or PCR HPV16 negative; T3-4N0-3M0 or T1-2N2-3M0 according to UICC/AJCC 8th staging system; Age =18; No prior anti-tumor treatment; Informed consent obtained; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Normal complete blood count; Normal hepatic function; Normal renal function (creatinine = 1.5 times the upper limit of normal). -

Exclusion Criteria:

Previous radiotherapy; A history of any other type of malignancy; Pregnancy or lactation; Obvious disfunction of liver, renal, cardiac or lung function; Un controlled infection; Systemic metastasis or distant metastasis; Patients with severe gastrointestinal diseases; Patients with mental disorders affecting patient participation in trial judgement.

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Related Conditions & MeSH terms

• Oropharyngeal Cancer
• Oropharyngeal Neoplasms

Intervention

Procedure:
• Toxicities reduced treatment
Two cycles toripalimab+docetaxel+cisplatin+capecitabine (TPF) induction chemotherapy followed by reducing radiation dose(60Gy/30Fx) and omitting concurrent cisplatin chemotherapy when responses to induction chemotherapy are = 70% Partial Response(PR) in HPV-related patients. Two cycles toripalimab+docetaxel+cisplatin+capecitabine (TPF) induction chemotherapy followed by reducing radiation dose(60Gy/30Fx) combined with concurrent cisplatin chemotherapy when responses to induction chemotherapy are = 70% Partial Response(PR) in HPV-urelated patients.
• Conventional treatment
Two cycles toripalimab+docetaxel+cisplatin+capecitabine (TPF) induction chemotherapy followed by concurrent cisplatin chemoradiotherapy with standard radiation dose (70.4Gy/32Fx) when responses to induction chemotherapy are less than 70% Partial Response (PR) regardless of HPV status.

Locations

Country	Name	City	State
China	Eye & ENT Hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	Objective Response Rate	2 year
Primary	LRRR	locoregional recurrence rate	2 year
Primary	PFS	progression free survival	2 year
Primary	OS	overall survival	2 year
Secondary	The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG	The incidence (percentage) of late toxicity , Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG.	2 year
Secondary	QoL	Quality of Life according to EORTC QLQ-C30	2 year
Secondary	Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG	The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG.	2 years