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

NCT04995120 | Unknown Phase 2 DMC

• 2 other identifiers: Larynx-IO 1.02103232-1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Laryngeal Cancer; Hypopharynx Cancer; Laryngeal Neoplasms

Keywords

Induction chemotherapy; Checkpoint inhibitor; PD-1 inhibitor; Toripalimab; Larynx preservation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Overall response rate of induction therapy

  2 weeks after the 3th cycle of induction therapy

• Overall response rate of treatment

  3 months post-radiotherapy

• Pathological complete response rate of the patients receiving surgical resection

  Within 3 weeks after surgery

• Major pathologic response rate of the patients receiving surgical resection

  Within 3 weeks after surgery

• Overall survival rate at 1 year

  One year post-radiotherapy

Other Outcomes (4)

• Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups

  3-month post-radiotherapy

• Overall response rate of induction therapy, by different biomarker subgroups

  2 weeks after the 3th cycle of induction therapy

• Pathological complete response rate by different biomarker subgroups

  Within 3 weeks after surgery

Study Arms (1)

Induction chemotherapy and Toripalimab

EXPERIMENTAL

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.

Drug: chemotherapy TP regimen combined with Toripalimab

Interventions

chemotherapy TP regimen combined with Toripalimab DRUG

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.

Also known as: Paclitaxel or Nab-Paclitaxel, Cisplatin

Induction chemotherapy and Toripalimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 26681800 BACKGROUND

• 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.

  PMID: 2034244 BACKGROUND

• 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.

  PMID: 23182993 BACKGROUND

• 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.

  PMID: 23341517 BACKGROUND

• 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.

  PMID: 30115475 BACKGROUND

MeSH Terms

Conditions

Laryngeal Neoplasms; Hypopharyngeal Neoplasms

Interventions

toripalimab; 130-nm albumin-bound paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Xiayun He, M.D.

  Fudan Universtiy Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

• Yu Wang, M.D.

  Fudan Universtiy Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiayun He, M.D.

CONTACT

(86)021-64175590; hexiayun1962@126.com

Yu Wang, M.D.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., professor

Study Record Dates

• First Submitted: July 25, 2021
• First Posted: August 6, 2021
• Study Start: April 7, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: January 18, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)