The Efficacy of Induction and Adjuvant Camrelizumab Combined With Chemoradiation for LA-HNSCC

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase II Trial of Induction and Adjuvant Camrelizumab Combined With Chemoradiation in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05213884
• Other study ID #: CRIA
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: May 2023
• Source: Chongqing University Cancer Hospital
• Contact: Xin Zhang, Ph.D, M.D.
• Phone: 18323063006
• Email: zhangxin9964[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 2, single-arm clinical trial, with the purpose to evaluate the therapeutic efficacy and safety of PD-1 Blockade camrelizumab combined with induction chemotherapy followed by concurrent chemoradiotherapy and as adjuvant monotherapy in patients with locally advanced head and neck squamous cell carcinoma.

Description:

All participants from 3 hospitals will receive induction camrelizumab therapy at least one cycle (every 3 weeks) followed by definitive concurrent chemoradiotherapy. After 4~6 weeks of the completion of radiotherapy, adjuvant camrelizumab therapy will begin every 3 weeks for 16 cycles (1 year) or continue until progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and females =18 years of age.

2. ECOG Performance Status 0 or 1.

3. Histological diagnosis of squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx, larynx or nasal sinus.

4. Stage III, IVa, IVb (according to the 8th AJCC edition); Stage III for HPV positive oropharyngeal disease.

5. Inoperable or refused surgery; eligible for definitive concurrent chemoradiotherapy.

6. With measurable target lesions by CT or MRI.

7. Adequate bone marrow function.

8. Adequate renal and liver function.

9. Pregnancy test (for patients of childbearing potential) negative at screening.

10. Signed Written Informed Consent.

Exclusion Criteria:

1. Have a history of immunodeficiency, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation.

2. Active autoimmune disease (Such as type I diabetes, vitiligo, psoriasis, patients who do not need immunosuppressive drugs do not need to be excluded).

3. Has abnormal thyroid function, and the thyroid function cannot be maintained normal despite medical treatment.

4. Pregnancy or breast feeding.

5. Has a history of psychiatric substance abuse, alcoholism, or drug addiction.

6. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent.

7. Has received a live vaccine within 4 weeks of planned start of study therapy.

8. Has hepatitis B surface antigen (HBsAg) positive with HBV DNA copy number of =1000cps/ml or hepatitis C virus (HCV) antibody positive.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Camrelizumab
200 mg, intravenous infusion over 30 minutes (Q3W); 1~3 cycles of camrelizumab before radiotherapy and camrelizumab are maintained for 16 cycles (1 year) after the end of radiotherapy.
• Concurrent cisplatin chemotherapy
cisplatin is given at a dose of 40 mg/m2 via intravenous infusion during radiotherapy and starts on the 1st day of radiotherapy every week for 6 cycles.

Radiation:
• Intensity-modulated radiotherapy (IMRT)
70 Gy/ 35 fractions/7 weeks, 5 fractions/week, 1 fraction/day.

Locations

Country	Name	City	State
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	The Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	Chongqing University Three Gorges Hospital	Wanzhou	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing University Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014 Sep 20;32(27):2940-50. doi: 10.1200/JCO.2013.53.5633. — View Citation

Bauml J, Seiwert TY, Pfister DG, Worden F, Liu SV, Gilbert J, Saba NF, Weiss J, Wirth L, Sukari A, Kang H, Gibson MK, Massarelli E, Powell S, Meister A, Shu X, Cheng JD, Haddad R. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol. 2017 May 10;35(14):1542-1549. doi: 10.1200/JCO.2016.70.1524. Epub 2017 Mar 22. — 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, Jin F, Rischin D; KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019 Nov 23;394(10212):1915-1928. doi: 10.1016/S0140-6736(19)32591-7. Epub 2019 Nov 1. Erratum In: Lancet. 2020 Jan 25;395(10220):272. Lancet. 2020 Feb 22;395(10224):564. Lancet. 2021 Jun 12;397(10291):2252. — View Citation

Lee NY, Ferris RL, Psyrri A, Haddad RI, Tahara M, Bourhis J, Harrington K, Chang PM, Lin JC, Razaq MA, Teixeira MM, Lovey J, Chamois J, Rueda A, Hu C, Dunn LA, Dvorkin MV, De Beukelaer S, Pavlov D, Thurm H, Cohen E. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):450-462. doi: 10.1016/S1470-2045(20)30737-3. — View Citation

Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016 Jul;17(7):956-965. doi: 10.1016/S1470-2045(16)30066-3. Epub 2016 May 27. — 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 L, Jo VY, Stachler MD, Hanna GJ, Kass J, Haddad R, Schoenfeld JD, Gjini E, Lako A, Thorstad W, Gay HA, Daly M, Rodig SJ, Hagemann IS, Kallogjeri D, Piccirillo JF, Chernock RD, Griffith M, Griffith OL, Adkins DR. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Clin Cancer Res. 2020 Oct 1;26(19):5140-5152. doi: 10.1158/1078-0432.CCR-20-1695. Epub 2020 Jul 14. Erratum In: Clin Cancer Res. 2021 Jan 1;27(1):357. — View Citation

Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8. Epub 2021 Jun 23. — View Citation

Zandberg DP, Strome SE. The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 2014 Jul;50(7):627-32. doi: 10.1016/j.oraloncology.2014.04.003. Epub 2014 May 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	EFFICACY Progress-free survival (PFS)	Defined as time from randomization to locoregional or distant metastasis relapse or death from any cause, whichever occurred first.	2 years
Secondary	EFFICACY Overall survival (OS)	Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive.	2 years
Secondary	EFFICACY Objective response rate (ORR)	Defined as a complete response (CR) or partial response (PR) from enrolled until disease progression or death due to any cause.	2 years
Secondary	EFFICACY Duration of response (DOR)	Defined as the time from the first assessment of CR or PR to the first assessment of disease progression or death due to any cause.	2 years
Secondary	SAFETY Incidence rate of adverse events (AEs)	Analysis of adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs, according to the Common Terminology Criteria for Adverse Events, version 5.0.	2 years
Secondary	QUALITY OF LIFE Quality of life (QoL): questionnaire	QoL is evaluated with the use of the head-and-neck-specific module (H&N35) of the Quality of Life Questionnaire-Core 30 module (QLQ-C30).	2 years