Clinical trial NCT04995120: Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma
Official title: Induction Chemotherapy and Toripalimab Followed by Surgery or Radiotherapy for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Laryngeal Cancer
Hypopharynx Cancer
Laryngeal Neoplasms
Keywords: Induction chemotherapy
Checkpoint inhibitor
PD-1 inhibitor
Toripalimab
Larynx preservation
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-08-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Laryngeal Preservation rate at 3-month post-radiotherapy
timeFrame: 3-month post-radiotherapy
Secondary outcomes:
measure: Overall response rate of induction therapy
timeFrame: 2 weeks after the 3th cycle of induction therapy
measure: Overall response rate of treatment
timeFrame: 3 months post-radiotherapy
measure: Pathological complete response rate of the patients receiving surgical resection
timeFrame: Within 3 weeks after surgery
measure: Major pathologic response rate of the patients receiving surgical resection
timeFrame: Within 3 weeks after surgery
measure: Overall survival rate at 1 year
timeFrame: One year post-radiotherapy
measure: Overall survival rate at 2 year
timeFrame: Two year post-radiotherapy
measure: Progression-free survival rate at 1 year
timeFrame: One year post-radiotherapy
measure: Progression-free survival rate at 2 year
timeFrame: Two year post-radiotherapy
measure: Laryngeal Preservation rate at 1 year
timeFrame: One year post-radiotherapy
measure: Laryngeal Preservation rate at 2 year
timeFrame: Two year post-radiotherapy
measure: Adverse Effect
timeFrame: One year post-radiotherapy
Other outcomes:
measure: Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups
timeFrame: 3-month post-radiotherapy
measure: Overall response rate of induction therapy, by different biomarker subgroups
timeFrame: 2 weeks after the 3th cycle of induction therapy
measure: Pathological complete response rate by different biomarker subgroups
timeFrame: Within 3 weeks after surgery
measure: Major pathologic response rate by different biomarker subgroups
timeFrame: Within 3 weeks after surgery
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan Universtiy Shanghai Cancer Center
name: Xiayun He, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan Universtiy Shanghai Cancer Center
name: Yu Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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):djv368. doi: 10.1093/jnci/djv368. Print 2016 Apr.
citation: 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. doi: 10.1056/NEJM199106133242402.
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.
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.
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.