PABLIXIMAB as Neoadjuvant Therapy for Head and Neck Squamous-cell Carcinoma

Immunotherapy Clinical Trial

Official title:

A Single-arm, Prospective, Phase II Study of PABLIXIMAB Combined With TP Chemotherapy as Neoadjuvant Therapy for Locally Advanced Head and Neck Squamous-cell Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06125223
• Other study ID #: KY20232325
• Status: Not yet recruiting
• Start date: November 1, 2023
• Est. completion date: November 1, 2026

Study information

• Verified date: November 2023
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this clinical trial is to learn about the efficacy and safety of pablizumab combined with neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma.

The main question it aims to answer is: Pathological complete remission (PCR) rate of tumor after neoadjuvant immunotherapy.

Participants will be asked to perform CT and MRI of head and neck, ultrasonography of cervical lymph nodes and necessary laboratory examinations Before and after neoadjuvant therapy. And will be following-up for at least 1 year.

Description:

The secondary questions it aims to answer are:

Objective response rate (ORR) after neoadjuvant therapy

• R0 resection rate

• major pathological remission (MPR) rate

• organ preservation rate

• event-free survival (EFS)

• local recurrence-free survival (LRFS)

• distant metastasis-free survival (DMFS)

• quality of life score (QoL)

• overall survival (OS)

• incidence of adverse events (including neoadjuvant stage AEs and full course AEs) The exploratory question it aims to answer is: clearance of peripheral blood ctDNA.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. age 18-80 years old, including 18 years old and 80 years old;

2. MRI diagnosis of resectable stage III-IVA oropharynx, larynx and hypopharynx squamous-cell carcinoma confirmed by histopathology or cytology;

3. ECOG PS score 0-1;

4. the expression of PD-L1 was detected by immunohistochemistry (TPS and CPS score)

5. having at least one measurable lesion according to RECIST version 1.1;

6. expected survival time =6 months;

7. The neutrophil count was =1.5 × 10^9/L, the platelet count was =100 × 10^9/L, the hemoglobin count was =90 g/L

8. renal function was normal: serum creatinine =1.5×ULN;

9. the liver function was basically normal: serum total bilirubin =1.5 × ULN, serum aspartate transaminase (AST)=2.5×ULN, serum Alanine transaminase (ALT)=2.5 ×ULN;

10. female patients had to be negative for a urine pregnancy test before the start of the study (not applicable to patients with bilateral oophorectomy and/or hysterectomy or postmenopausal patients) ;

11. Sign the written informed consent.

Exclusion Criteria:

1. patients were treated with anti-tumor drugs including but not limited to PD-1 inhibitor, CTLA-4 antibody, EGFR monoclonal antibody, EGFR-tki, and anti-angiogenesis drugs;

2. History of autoimmune diseases including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, Rheumatoid Arthritis, inflammatory bowel disease, Antiphospholipid syndrome vascular thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis.

3. participated in other intervention clinical trials within 30 days before screening;

4. history of other malignancies (except cured skin basal-cell carcinoma) ;

5. the presence of serious and poorly controlled co-morbidities (e.g. heart failure, diabetes, hypertension, liver failure, kidney failure, thyroid disease, mental illness, etc.) ;

6. Known to be infected with HIV or active hepatitis or tuberculosis;

7. major surgery or planned surgery within 30 days before the first dose of the trial drug;

8. Persons who are allergic to the use of drugs or their components in the programme;

9. pregnancy (confirmed by blood or urine HCG testing) or lactation in women, or in subjects of reproductive age who were unwilling or unable to use effective contraception (for both male and female subjects) until at least 6 months after the last trial treatment;

10. it is not suitable for the researcher to participate in this study;

11. Unwilling to participate in the study or unable to sign the informed consent.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Immunotherapy
• Neoadjuvant Therapy
• Squamous Cell Carcinoma of Head and Neck

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

References & Publications (12)

Bhatia A, Burtness B. Treating Head and Neck Cancer in the Age of Immunotherapy: A 2023 Update. Drugs. 2023 Feb;83(3):217-248. doi: 10.1007/s40265-023-01835-2. Epub 2023 Jan 16. — View Citation

Burtness B, Harrington KJ, Greil R, Soulieres D, Tahara M, de Castro G Jr, Psyrri A, Baste N, Neupane P, Bratland A, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, Gonzalez Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD — View Citation

Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, Birkeland AC, Brizel DM, Busse PM, Cmelak AJ, Colevas AD, Eisele DW, Galloway T, Geiger JL, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Mell LK, Mittal BB, Pinto HA, Rocco JW — View Citation

Diaz LA Jr, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fourchardiere C, Rivera F, Elez E, Le DT, Yoshino T, Zhong WY, Fogelman D, Marinello P, Andre T; KEYNOTE-177 Investigators. Pembrolizumab v — View Citation

Ferris RL, Spanos WC, Leidner R, Goncalves A, Martens UM, Kyi C, Sharfman W, Chung CH, Devriese LA, Gauthier H, Chiosea SI, Vujanovic L, Taube JM, Stein JE, Li J, Li B, Chen T, Barrows A, Topalian SL. Neoadjuvant nivolumab for patients with resectable HPV — View Citation

Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph R, Weber JS, Dronca R, Mitchell TC, Patnaik A, Zarour HM, Joshua AM, Zhao Q, Jensen E, Ahsan S, Ibrahim N, Ribas A. Five-year survival outcomes for patients with advanced — View Citation

Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020 Nov 26;6(1):92. doi: 10.1038/s41572-020-00224-3. Erratum In: Nat Rev Dis Primers. 2023 Jan 19;9(1):4. — View Citation

Keam B, Machiels JP, Kim HR, Licitra L, Golusinski W, Gregoire V, Lee YG, Belka C, Guo Y, Rajappa SJ, Tahara M, Azrif M, Ang MK, Yang MH, Wang CH, Ng QS, Wan Zamaniah WI, Kiyota N, Babu S, Yang K, Curigliano G, Peters S, Kim TW, Yoshino T, Pentheroudakis — View Citation

Oliva M, Spreafico A, Taberna M, Alemany L, Coburn B, Mesia R, Siu LL. Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma. Ann Oncol. 2019 Jan 1;30(1):57-67. doi: 10.1093/annonc/mdy507. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caa — View Citation

Uppaluri R, Campbell KM, Egloff AM, Zolkind P, Skidmore ZL, Nussenbaum B, Paniello RC, Rich JT, Jackson R, Pipkorn P, Michel LS, Ley J, Oppelt P, Dunn GP, Barnell EK, Spies NC, Lin T, Li T, Mulder DT, Hanna Y, Cirlan I, Pugh TJ, Mudianto T, Riley R, Zhou — View Citation

Veigas F, Mahmoud YD, Merlo J, Rinflerch A, Rabinovich GA, Girotti MR. Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma. Cancers (Basel). 2021 Mar 1;13(5):1018. doi: 10.3390/cancers13051018. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	clearance of peripheral blood ctDNA	ctDNA is circulating tumor DNA, also known as tumor DNA, which enters the bloodstream when tumor cells die or are released. It is a liquid biopsy method that detects the presence and associated changes of tumor cells in a blood sample.	At least 1 year.
Primary	Pathological complete remission (pCR) rate of tumor after neoadjuvant immunotherapy.	pCR means that there are no residual living tumor cells in the tumor bed and lymph nodes after neoadjuvant therapy.	About 50 days after the start of neoadjuvant immunotherapy.
Secondary	ORR(objective response rate)	Objective response rates after neoadjuvant immunotherapy were measured, usually as the proportion of patients whose tumor volume decreased by 30% and maintained over 4 weeks, that is, the sum of the rates of complete response (CR) and partial response (PR) , the higher the ORR, the more patients achieved tumor shrinkage with the treatment.	At least 1 year.
Secondary	R0 resection rate	R0 resection is the highest standard of tumor resection, which means complete tumor resection with negative margin. The tumor R0 resection rate was calculated for the patients who underwent surgery after the completion of neoadjuvant immunotherapy.	At least 1 year.
Secondary	MPR(major pathological response)	MPR is defined as the percentage of residual tumor cells in the tumor bed being less than or equal to 10% .	At least 1 year.
Secondary	Overall survival rate	Overall survival is the proportion of all participants who survived the study period. Overall survival was calculated by dividing the number of people alive by the total number at the start of the study.	At least 1 year.
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Researchers should grade the severity of each adverse event. If the severity/intensity of an adverse event is not specified in the guidelines, the investigator can assess it based on the general definition of grade 1-5 and in conjunction with his or her medical judgment.	At least 1 year.