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

Primary Purpose

Laryngeal Cancer, Hypopharynx Cancer, Laryngeal Neoplasms

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
chemotherapy TP regimen combined with Toripalimab
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Laryngeal Cancer focused on measuring Induction chemotherapy, Checkpoint inhibitor, PD-1 inhibitor, Toripalimab, Larynx preservation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Induction chemotherapy and Toripalimab

Arm Description

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 ORR of primary tumor is CR/PR, 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.

Outcomes

Primary Outcome Measures

Laryngeal Preservation rate at 3-month post-radiotherapy
defined as the absence of any residual disease that would justify salvage total laryngectomy

Secondary Outcome Measures

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
Overall response rate of treatment
Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria
Pathological complete response rate of the patients receiving surgical resection
Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists
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.
Overall survival rate at 1 year
Overall survival rate at 1 year
Overall survival rate at 2 year
Overall survival rate at 2 year
Progression-free survival rate at 1 year
Progression-free survival rate at 1 year
Progression-free survival rate at 2 year
Progression-free survival rate at 2 year
Laryngeal Preservation rate at 1 year
Laryngeal Preservation rate at 1 year
Laryngeal Preservation rate at 2 year
Laryngeal Preservation rate at 2 year
Adverse Effect
Adverse Effect, evaluated by CTCAE 4.0.03

Full Information

First Posted
July 25, 2021
Last Updated
January 2, 2022
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT04995120
Brief Title
Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma
Acronym
INSIGHT
Official Title
Induction Chemotherapy and Toripalimab Followed by Surgery or Radiotherapy for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 7, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Laryngeal Cancer, Hypopharynx Cancer, Laryngeal Neoplasms
Keywords
Induction chemotherapy, Checkpoint inhibitor, PD-1 inhibitor, Toripalimab, Larynx preservation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Induction chemotherapy and Toripalimab
Arm Type
Experimental
Arm Description
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 ORR of primary tumor is CR/PR, 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.
Intervention Type
Drug
Intervention Name(s)
chemotherapy TP regimen combined with Toripalimab
Other Intervention Name(s)
Paclitaxel or Nab-Paclitaxel, Cisplatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Laryngeal Preservation rate at 3-month post-radiotherapy
Description
defined as the absence of any residual disease that would justify salvage total laryngectomy
Time Frame
3-month post-radiotherapy
Secondary Outcome Measure Information:
Title
Overall response rate of induction therapy
Description
Overall response rate of induction therapy evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria
Time Frame
2 weeks after the 3th cycle of induction therapy
Title
Overall response rate of treatment
Description
Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria
Time Frame
3 months post-radiotherapy
Title
Pathological complete response rate of the patients receiving surgical resection
Description
Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists
Time Frame
Within 3 weeks after surgery
Title
Major pathologic response rate of the patients receiving surgical resection
Description
Major pathologic response rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists.
Time Frame
Within 3 weeks after surgery
Title
Overall survival rate at 1 year
Description
Overall survival rate at 1 year
Time Frame
One year post-radiotherapy
Title
Overall survival rate at 2 year
Description
Overall survival rate at 2 year
Time Frame
Two year post-radiotherapy
Title
Progression-free survival rate at 1 year
Description
Progression-free survival rate at 1 year
Time Frame
One year post-radiotherapy
Title
Progression-free survival rate at 2 year
Description
Progression-free survival rate at 2 year
Time Frame
Two year post-radiotherapy
Title
Laryngeal Preservation rate at 1 year
Description
Laryngeal Preservation rate at 1 year
Time Frame
One year post-radiotherapy
Title
Laryngeal Preservation rate at 2 year
Description
Laryngeal Preservation rate at 2 year
Time Frame
Two year post-radiotherapy
Title
Adverse Effect
Description
Adverse Effect, evaluated by CTCAE 4.0.03
Time Frame
One year post-radiotherapy
Other Pre-specified Outcome Measures:
Title
Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups
Description
Experimental Biomarker Analysis: the relationship with different biomarkers and 3 month laryngeal preservation rate
Time Frame
3-month post-radiotherapy
Title
Overall response rate of induction therapy, by different biomarker subgroups
Description
Experimental Biomarker Analysis: the relationship with different biomarkers and overall response rate of induction therapy
Time Frame
2 weeks after the 3th cycle of induction therapy
Title
Pathological complete response rate by different biomarker subgroups
Description
Experimental Biomarker Analysis: the relationship with different biomarkers and pathological complete response rate of the patients receiving surgical resection
Time Frame
Within 3 weeks after surgery
Title
Major pathologic response rate by different biomarker subgroups
Description
Experimental Biomarker Analysis: the relationship with different biomarkers and major pathologic response rate of the patients receiving surgical resection
Time Frame
Within 3 weeks after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiayun He, M.D.
Phone
(86)021-64175590
Ext
81400
Email
hexiayun1962@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Wang, M.D.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiayun He, M.D.
Organizational Affiliation
Fudan Universtiy Shanghai Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Yu Wang, M.D.
Organizational Affiliation
Fudan Universtiy Shanghai Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiayun He, MD
Phone
+86-18017312167
Email
hexiayun1962@126.com
First Name & Middle Initial & Last Name & Degree
Xiaomin Ou, MD
Phone
+86-18017317872
Email
0456218@fudan.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26681800
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.
Results Reference
background
PubMed Identifier
2034244
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.
Results Reference
background
PubMed Identifier
23182993
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.
Results Reference
background
PubMed Identifier
23341517
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.
Results Reference
background
PubMed Identifier
30115475
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.
Results Reference
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Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

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