Clinical trial NCT06156891: PD-1 Inhibitor Based Induction Chemotherapy Followed by De-escalation Protocols in OPSCC
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oropharyngeal Cancer
Keywords: Oropharyngeal Cancer
Immune Checkpoint Inhibitor
Induction chemotherapy
De-escalation
HPV-related
HPV-unrelated
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-12-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

-

Primary outcomes:
measure: ORR
timeFrame: 2 year
measure: LRRR
timeFrame: 2 year
measure: PFS
timeFrame: 2 year
measure: OS
timeFrame: 2 year
Secondary outcomes:
measure: The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG
timeFrame: 2 year
measure: QoL
timeFrame: 2 year
measure: Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG
timeFrame: 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eye & ENT Hospital of Fudan University
state: Shanghai
Study officials:
References: