Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

Laryngeal Cancer Clinical Trial

— INSIGHT  

Official title:

Induction Chemotherapy and Toripalimab Followed by Surgery or Radiotherapy for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04995120
• Other study ID #: Larynx-IO 1.0
• Secondary ID: 2103232-1
• Status: Recruiting
• Phase: Phase 2
• Start date: April 7, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2022
• Source: Fudan University
• Contact: Xiayun He, M.D.
• Phone: (86)021-64175590
• Email: hexiayun1962[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Description:

Historically, induction chemotherapy could provide a chance of larynx preservation for approximate 60-70% of patients with locally advanced laryngeal/hypopharyngeal carcinoma. Recently, phase I-II clinical studies demonstrated excellent pathological response of induction PD-1 inhibitor with/without chemotherapy for locally advanced head and neck cancer. The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma (T2-4a, N0-resectable N3, M0);

• Age between 18-75 years;

• Signed inform consent;

• Had at least one measurable lesion according to RECIST 1.1 criteria

• Anticipated overall survival more than 3 months;

• Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1;

• Normal organ function;

• HBV DNA<500 IU/mL(or 2500 copies/mL)and HCV RNA negative ;

• Male and no pregnant female, able to adapt birth control methods during treatment.

Exclusion Criteria:

• Hypersensitivity to Toripalimab, Paclitaxel, Nab-Paclitaxel and Cisplatin;

• Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years;

• Severe, uncontrolled heart disease;

• Receive vaccine or live vaccine within 28 days prior to signing the informed consent;

• Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent;

• Surgery or trauma within 28 days prior to signing the informed consent;

• Received other immune checkpoint inhibitors previously;

• Severe, uncontrolled infections within 28 days of prior to signing the informed consent;

• Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, vitiligo or inactive asthma who don't need systemic therapy can recruit;

• History of interstitial lung disease;

• HIV positive;

• Hepatitis B surface antigen (HBsAg) positive and HBV-DNA =500IU/ml, or 2500cps/ml; Positive HCV RNA;

• Other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors;

• Women of child-bearing potential who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Hypopharynx Cancer
• Laryngeal Cancer
• Laryngeal Neoplasms

Intervention

Drug:
• chemotherapy TP regimen combined with Toripalimab
Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2 or Nab-Paclitaxel 260mg/m2 d2,Cisplatin 25mg/m2 d2-4 q3w. Response rate of primary tumor is evaluated using laryngoscopy and head and neck MRI after 3 cycles of induction therapy. If overall response rate of primary tumor is complete response or partial response, then chemoradiation is conducted, followed by maintenance therapy of Toripalimab for 8 cycles (6 months). Otherwise, surgery is conducted (laryngeal preservation surgery is preferred), followed by adjuvant radiation/chemoradiation and then maintenance therapy of Toripalimab for 8 cycles.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (5)

Department of Veterans Affairs Laryngeal Cancer Study Group, Wolf GT, Fisher SG, Hong WK, Hillman R, Spaulding M, Laramore GE, Endicott JW, McClatchey K, Henderson WG. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991 Jun 13;324(24):1685-90. — View Citation

Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 26. — View Citation

Janoray G, Pointreau Y, Garaud P, Chapet S, Alfonsi M, Sire C, Jadaud E, Calais G. Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation. J Natl Cancer Inst. 2015 Dec 16;108(4). pii: djv368. doi: 10.1093/jnci/djv368. Print 2016 Apr. — View Citation

Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. doi: 10.1200/JCO.2012.42.3988. Epub 2013 Jan 22. Erratum in: J Clin Oncol. 2013 May 1;31(13):1702. — View Citation

Weiss J, Gilbert J, Deal AM, Weissler M, Hilliard C, Chera B, Murphy B, Hackman T, Liao JJ, Grilley Olson J, Hayes DN. Induction chemotherapy with carboplatin, nab-paclitaxel and cetuximab for at least N2b nodal status or surgically unresectable squamous cell carcinoma of the head and neck. Oral Oncol. 2018 Sep;84:46-51. doi: 10.1016/j.oraloncology.2018.06.028. Epub 2018 Jul 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups	Experimental Biomarker Analysis: the relationship with different biomarkers and 3 month laryngeal preservation rate	3-month post-radiotherapy
Other	Overall response rate of induction therapy, by different biomarker subgroups	Experimental Biomarker Analysis: the relationship with different biomarkers and overall response rate of induction therapy	2 weeks after the 3th cycle of induction therapy
Other	Pathological complete response rate by different biomarker subgroups	Experimental Biomarker Analysis: the relationship with different biomarkers and pathological complete response rate of the patients receiving surgical resection	Within 3 weeks after surgery
Other	Major pathologic response rate by different biomarker subgroups	Experimental Biomarker Analysis: the relationship with different biomarkers and major pathologic response rate of the patients receiving surgical resection	Within 3 weeks after surgery
Primary	Laryngeal Preservation rate at 3-month post-radiotherapy	defined as the absence of any residual disease that would justify salvage total laryngectomy	3-month post-radiotherapy
Secondary	Overall response rate of induction therapy	Overall response rate of induction therapy evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria	2 weeks after the 3th cycle of induction therapy
Secondary	Overall response rate of treatment	Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria	3 months post-radiotherapy
Secondary	Pathological complete response rate of the patients receiving surgical resection	Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists	Within 3 weeks after surgery
Secondary	Major pathologic response rate of the patients receiving surgical resection	Major pathologic response rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists.	Within 3 weeks after surgery
Secondary	Overall survival rate at 1 year	Overall survival rate at 1 year	One year post-radiotherapy
Secondary	Overall survival rate at 2 year	Overall survival rate at 2 year	Two year post-radiotherapy
Secondary	Progression-free survival rate at 1 year	Progression-free survival rate at 1 year	One year post-radiotherapy
Secondary	Progression-free survival rate at 2 year	Progression-free survival rate at 2 year	Two year post-radiotherapy
Secondary	Laryngeal Preservation rate at 1 year	Laryngeal Preservation rate at 1 year	One year post-radiotherapy
Secondary	Laryngeal Preservation rate at 2 year	Laryngeal Preservation rate at 2 year	Two year post-radiotherapy
Secondary	Adverse Effect	Adverse Effect, evaluated by CTCAE 4.0.03	One year post-radiotherapy