Oropharyngeal Cancer
Conditions
Keywords
Oropharyngeal Cancer, Immune Checkpoint Inhibitor, Induction chemotherapy, De-escalation, HPV-related, HPV-unrelated
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.
Interventions
PROCEDUREToxicities 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.
PROCEDUREConventional 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.
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 2 year | Objective Response Rate |
| LRRR | 2 year | locoregional recurrence rate |
| PFS | 2 year | progression free survival |
| OS | 2 year | overall survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QoL | 2 year | Quality of Life according to EORTC QLQ-C30 |
| Number and percentage of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and RTOG | 2 years | The detail number and percentage of adverse events by every systems Assessed by CTCAE v5.0 and RTOG. |
| The percentage of Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG | 2 year | The incidence (percentage) of late toxicity , Grade 3 and 4 adverse reactions in NCI-CTC AE 5.0 and RTOG. |
Countries
China
Contacts
Primary ContactXiaoshen Wang, MD, Ph.D
Backup ContactRuichen Li, MD
Outcome results
None listed