Toripalimab in Combination With Chemotherapy as Induced Chemotherapy for Localized Hypopharyngeal Cancer

NCT04296747 | Unknown Phase 2 DMC

• 1 other identifier: JS001-ISS-CO159
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

60% of hypopharyngeal cancers were locally advanced at the time of diagnosis. The standard treatment was surgery and postoperative radiotherapy. Compared with traditional surgery and postoperative radiotherapy, induction chemotherapy combined with radiotherapy has a better laryngeal retention rate without reducing the curative effect, and established an organ function preservation treatment strategy. Induction chemotherapy can reduce tumor burden and reduce distant metastases. At present, induction chemotherapy followed by concurrent chemoradiotherapy has become the standard treatment for the laryngeal preservation in locally advanced hypopharyngeal and laryngeal cancer. This study aimed to investigate the efficacy and safety of a PD-1 inhibitor toripalimab combined with chemotherapy as induction therapy in hypopharyngeal cancer.

Conditions

Hypopharyngeal Squamous Cell Carcinoma

Keywords

Toripalimab, hypopharyngeal cancer, induction therapy

Outcome Measures

Primary Outcomes (1)

• overall objective rate

  the percentage of patients whose best overall response was confirmed complete or partial response

  Up to 2 year

Secondary Outcomes (5)

• major pathologic response

  Up to 2 year

• 2-year overall survival rate

  Up to 2 years

• 2-year progression-free survival rate

  Up to 2 years

• 2-year disease-free survival rate

  Up to 2 years

• EORTC H&N 35 form evaluated quality of life

  Up to 2 years

Study Arms (1)

Induction therapy

EXPERIMENTAL

patients would accept toripalimab combined with chemotherapy as induction therapy, then radical treatment(surgery or chemoradiotherapy) according to whether the tumor could be resectable or the evaluation result according to RECIST1.1. Ones with PD after induction therapy will enter survival follow-up directly

Drug: induction chemotherapy; Procedure: surgery; Radiation: chemoradiotherapy

Interventions

induction chemotherapy DRUG

Toripalimab 240mg, d1; docetaxel 75mg/m2 d1; cisplatin 75mg/m2 d1, q21d, for 2 cycles

Induction therapy

surgery PROCEDURE

After induction chemotherapy, patients with resectable hypopharyngeal cancer would accept surgery within 2-4 weeks and investigator-selected postoperative treatment

Induction therapy

chemoradiotherapy RADIATION

After induction chemotherapy, patients with unresectable hypopharyngeal cancer who achieved CR/PR/SD in the tumor evaluation according to RECIST1.1 would accept another cycle of chemotherapy, and then radical chemoradiotherapy with cisplatin 100mg/m2, q21d

Induction therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years when signing informed consent.
• Pathopharyngeal (histological) confirmed hypopharyngeal squamous cell carcinoma.
• The initial diagnosis is T1N + M0, T2-4 anyNM0 according to the 8th edition of AJCC.
• Patients who is suitable and agrees to radical treatment.
• With evaluable lesions according to the RECIST version 1.1. Note: According to the RECIST 1.1, evaluable lesions refers to a lesion that has been previously treated with radiotherapy. If a clear tumor progression appearance then, it can be used as a measurable lesion.
• ECOG PS ≤1
• Adequate organ function, defined as achieving the following laboratory test results ≤ 14 days before treatment
• a. Patients must meet the following laboratory test results: i. ANC ≥ 1.5 x 109 / L ii. Platelets ≥100 x 109 / L iii. Hb ≥90 g / L
• Note: Patients must not receive blood transfusion or growth factor within 14 days before blood sample collection due to neutrophil count, platelet, or hemoglobin below study requirements.
• Renal function requirements within 4 weeks before treatment: Endogenous creatinine clearance ≥ 60 mL / min or more (based on 24-hour urine creatinine calculation or Cockcroft-Gault formula method).
• Serum total bilirubin ≤ 1.5×ULN (Gilbert syndrome patients can be enrolled if the total bilirubin is \<3 × ULN).
• AST and ALT ≤ 3 × ULN. If the patient has liver metastases, AST and ALT ≤ 5×ULN.
• Patients with hepatitis B virus (HBV) infection and inactive / asymptomatic HBV carriers; or patients with chronic or active HBV, if HBV DNA \<500 IU / mL (or 2500 copies/ mL) will be allowed to enroll. Hepatitis C antibody-positive patients will be allowed to enroll if HCV-RNA is negative during screening.
• NOTE: Patients with detect hepatitis B surface antigen (HBsAg) or HBV DNA, and patients receiving antiviral therapy during screening should be treated for\> 2 weeks before enrollment, and Continue treatment for 6 months after study drug therapy
• Women of childbearing age (WOCBP) must be willing to take effective contraception during the study period and ≥60 days after the last study treatment (including chemotherapy) administration, and the urine or serum pregnancy test result is negative within ≤7 days before treatment.

You may not qualify if:

• Not suitable for any of the two-drug chemotherapy prescribed in the protocol
• Have previously received any treatment for hypopharyngeal squamous cell carcinoma.
• Patients with evidence of fistula (esophagus / bronchus or esophagus / aorta)
• Presence of uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage or medical intervention (with clinically significant recurrence requiring additional intervention within 2 weeks after the intervention).
• Evidence of complete esophageal obstruction that is not suitable for treatment
• Have been treated with antitumor agents targeted to PD-1, PD-L1 or PD-L2.
• Have active meningeal disease or uncontrolled brain metastases:
• a. Patients with a history of CNS metastasis while be asymptomatic at the time of screening can be recruit as long as they meet all the following conditions: i. Patients without immediate radiological progression, which means disease progression happened between two consecutive assessments (1 month interval) ii. There are evaluable lesions outside CNS. iii. No need for continuous use of glucocorticoids to treat CNS disease; stable doses of anticonvulsants would be allowed.
• iv. No stereotactic or whole brain radiotherapy was performed within 14 days before treatment.
• b. Patients with new asymptomatic CNS metastases that need to be treated with radiation and / or surgery and have completed corticosteroid therapy.
• i. After treatment, these patients are eligible as long as they meet all other criteria, including those with brain metastases.
• Patients with active autoimmune disease or history of autoimmune diseases may relapse.
• Note: Patients with the following diseases can be entered for further screening:
• Controllable type 1 diabetes
• Hypothyroidism (only if it could be controlled by hormone replacement therapy)

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Hypopharyngeal Neoplasms

Interventions

Induction Chemotherapy; Surgical Procedures, Operative; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction; Combined Modality Therapy; Radiotherapy

Study Officials

• Chunmei Bai

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

Chunmei Bai, doctor

CONTACT

8601069156114; baichunmei1964@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: March 5, 2020
• Study Start: March 1, 2020
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2023
• Last Updated: March 5, 2020

Record last verified: 2020-02