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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Oropharyngeal Cancer
• Intervention / Treatment: Procedure: Toxicities reduced treatment; Procedure: Conventional treatment

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoshen Wang, MD, Ph.D; Phone Number: +8618917785187 18917785187; Email: xiaoshen.wang@fdeent.org
• Study Contact Backup: Name: Ruichen Li, MD; Phone Number: 17317822194; Email: liruichensogou@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Eye & ENT Hospital of Fudan University
      • Principal Investigator: Xiaoshen Wang
      • Contact: Xiaoshen Wang, MD, Ph.D; Phone Number: 18917785187; Email: xiaoshen.wang@fdeent.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toxicities reduced treatment arm; 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.	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.
Active Comparator: Conventional treatment arm; 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.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	2 year
LRRR	locoregional recurrence rate	2 year
PFS	progression free survival	2 year
OS	overall survival	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
QoL	Quality of Life according to EORTC QLQ-C30	2 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): July 30, 2025

Study Registration Dates

• First Submitted: November 26, 2023
• First Submitted That Met QC Criteria: November 26, 2023
• First Posted (Estimated): December 5, 2023

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Oropharyngeal Cancer; De-escalation; Induction chemotherapy; Immune Checkpoint Inhibitor; HPV-related; HPV-unrelated
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Oropharyngeal Neoplasms
• Other Study ID Numbers: 2022145-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No