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

Primary Purpose

Hypopharyngeal Squamous Cell Carcinoma

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
induction chemotherapy
surgery
chemoradiotherapy
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypopharyngeal Squamous Cell Carcinoma focused on measuring Toripalimab, hypopharyngeal cancer, induction therapy

Eligibility Criteria

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

Inclusion Criteria:

  1. Age ≥ 18 years when signing informed consent.
  2. Pathopharyngeal (histological) confirmed hypopharyngeal squamous cell carcinoma.
  3. The initial diagnosis is T1N + M0, T2-4 anyNM0 according to the 8th edition of AJCC.
  4. Patients who is suitable and agrees to radical treatment.
  5. 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.
  6. ECOG PS ≤1
  7. 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

    1. 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.
    2. 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).
    3. Serum total bilirubin ≤ 1.5×ULN (Gilbert syndrome patients can be enrolled if the total bilirubin is <3 × ULN).
    4. AST and ALT ≤ 3 × ULN. If the patient has liver metastases, AST and ALT ≤ 5×ULN.
  8. 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

  9. 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.

    a. Women of childbearing age are defined as any woman who has had menarche and has not undergone sterilization (hysterectomy or bilateral ovariectomy) and has not yet reached menopause. Menopause is defined as amenorrhea for 12 months in women> 45 without other biological or physiological causes. In addition, to confirm menopause, women under 55 must have serum follicle stimulating hormone (FSH) levels> 40 mIU / mL.

  10. Unsterilized male must be willing to take effective contraception during the study and ≥ 60 days after the last study treatment (including chemotherapy) was administered.

Exclusion Criteria:

  1. Not suitable for any of the two-drug chemotherapy prescribed in the protocol
  2. Have previously received any treatment for hypopharyngeal squamous cell carcinoma.
  3. Patients with evidence of fistula (esophagus / bronchus or esophagus / aorta)
  4. 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).
  5. Evidence of complete esophageal obstruction that is not suitable for treatment
  6. Have been treated with antitumor agents targeted to PD-1, PD-L1 or PD-L2.
  7. 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.

  8. Patients with active autoimmune disease or history of autoimmune diseases may relapse.

    Note: Patients with the following diseases can be entered for further screening:

    1. Controllable type 1 diabetes
    2. Hypothyroidism (only if it could be controlled by hormone replacement therapy)
    3. Controlled celiac disease
    4. Skin diseases that do not require systemic treatment (eg vitiligo, psoriasis, hair loss)
    5. Any other disease that is not expected to recur without external triggers
  9. Any active malignancy within ≤ 2 years before treatment, expect specific cancers which being studied in this study and locally recurrent cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical cancer and breast cancer in situ).
  10. Any condition requiring systemic treatment with corticosteroids (dose above 10 mg / day of prednisone or equivalent dose of similar agents) or other immunosuppressive agents within ≤ 14 days prior to treatment.

    Note: Patients who are currently or previously using any of the following steroid regimens can be enrolled:

    1. Adrenaline replacement (prednisone ≤10mg / day or equivalent dose of similar agents)
    2. Local, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids with minimal systemic absorption.
    3. Prophylactic short-term (≤7 days) use of corticosteroids (for example, to prevent hypersensitivity caused by contrast agent) or to treat non-autoimmune conditions (for example, delayed-type hypersensitivity reactions caused by exposure to allergens).
  11. Have a history of interstitial lung disease, non-infectious pneumonia or uncontrolled disease including pulmonary fibrosis, acute lung disease, etc.
  12. Severe chronic or active infections (including tuberculosis infections, etc.) that require systemic antibacterial, antifungal, or antiviral treatment within 14 days of treatment.
  13. History of HIV infection.
  14. Underwent any major surgery requiring general anesthesia ≤ 28 days before treatment.
  15. Previously allogeneic stem cell transplantation or organ transplantation.
  16. Have any of the following cardiovascular risk factors:

    1. Cardiogenic chest pain occurs within ≤ 28 days prior to treatment and is defined as moderate pain that limits applianceal activities of daily life.
    2. Symptomatic pulmonary embolism occurred within ≤ 28 days before treatment
    3. Acute myocardial infarction occurred within 6 months before treatment
    4. History of heart failure that has reached New York Heart Association Class III or IV ≤ 6 months before treatment.
    5. Ventricular arrhythmia of grade ≥ 2 occurred within ≤ 6 months before treatment
    6. Cerebrovascular accident occurred within ≤ 6 months before treatment
    7. Uncontrolled hypertension: SBP ≥160 mmHg or DBP ≥100 mmHg, although antihypertensive drugs were used ≤ 28 days before treatment or before the first study drug
    8. Any syncope or convulsions ≤ 28 days before treatment
  17. History of severe hypersensitivity to other monoclonal antibodies.
  18. Have received Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before the first study drug administration.
  19. Live vaccinations within ≤ 4 weeks before treatment. Note: Seasonal flu vaccines are usually inactivated vaccines and are allowed. The vaccine used in the nasal cavity is a live vaccine and is not allowed.
  20. Presence of basic medical conditions (including abnormal laboratory test values) or alcohol / drug abuse or dependence that are detrimental to study drug administration or affect drug toxicity or AE interpretation, or that may reduce compliance during the study .
  21. Participate in another therapeutic clinical trial at the same time
  22. Unintentional weight loss ≥ 5% within 1 month before treatment or severe malnutrition.
  23. Nutritional risk index (Shirasu et al 2018) can be used to determine severe malnutrition
  24. Pregnant or lactating women
  25. peripheral neuropathy ≥ grade 2 at baseline
  26. Uncontrolled diabetes, abnormalities of laboratory tests in potassium, sodium or corrected calcium>grade 1 despite standard medication,or hypoalbuminemia ≥ grade 3 within 14 days before treatment.
  27. Have received any chemotherapy, immunotherapy (eg interleukin, interferon, thymosin) or any research treatment within 14 days or 5 half-lives (whichever is longer) before the first study drug administration.
  28. Other exclusion criteria

    1. Prisoner or jailer.
    2. People who have been compulsorily detained for the treatment of a mental or physical illness, such as an infectious disease.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Induction therapy

    Arm Description

    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

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    major pathologic response
    the percentage of patients whose postoperative pathology showing surviving tumor cells ≤10%
    2-year overall survival rate
    the percentage of patients who survived at 2 year from the first dose
    2-year progression-free survival rate
    the percentage of patients who accepted chemoradiotherapy and survived without initial radiological progression or death from any cause at 2 year from the first dose
    2-year disease-free survival rate
    the percentage of patients who accepted surgery and survived without the first appearance of disease or death from any cause at 2 year from the first dose
    EORTC H&N 35 form evaluated quality of life
    EORTC H&N 35 form evaluated quality of life

    Full Information

    First Posted
    March 3, 2020
    Last Updated
    March 3, 2020
    Sponsor
    Peking Union Medical College Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04296747
    Brief Title
    Toripalimab in Combination With Chemotherapy as Induced Chemotherapy for Localized Hypopharyngeal Cancer
    Official Title
    A Single-arm Study Evaluating Efficacy and Safety of Toripalimab Combined With Docetaxel and Cisplatin as Induced Chemotherapy in the Treatment of Localized Hypopharyngeal Squamous Cell Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 2020 (Anticipated)
    Primary Completion Date
    March 2022 (Anticipated)
    Study Completion Date
    March 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Peking Union Medical College Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    Detailed Description
    This is a phase II, multicenter, open-label, single-arm study, planned to enroll 100 patients with localized hypopharyngeal squamous cell carcinoma who are newly treated and could accept radical treatment. Patients would be treated with toripalimab combined with docetaxel and cisplatin for two cycles. After the induction chemotherapy is completed, the investigator choose appropriate radical treatment (surgery or chemoradiotherapy) based on tumor evaluation. The primary endpoint is overall objective rate (ORR), the second endpoint include major pathologic response (MPR), 2-year DFS for surgery patients, 2-year PFS for radiotherapy patients, OS and QOL.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hypopharyngeal Squamous Cell Carcinoma
    Keywords
    Toripalimab, hypopharyngeal cancer, induction therapy

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Induction therapy
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    induction chemotherapy
    Intervention Description
    Toripalimab 240mg, d1; docetaxel 75mg/m2 d1; cisplatin 75mg/m2 d1, q21d, for 2 cycles
    Intervention Type
    Procedure
    Intervention Name(s)
    surgery
    Intervention Description
    After induction chemotherapy, patients with resectable hypopharyngeal cancer would accept surgery within 2-4 weeks and investigator-selected postoperative treatment
    Intervention Type
    Radiation
    Intervention Name(s)
    chemoradiotherapy
    Intervention Description
    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
    Primary Outcome Measure Information:
    Title
    overall objective rate
    Description
    the percentage of patients whose best overall response was confirmed complete or partial response
    Time Frame
    Up to 2 year
    Secondary Outcome Measure Information:
    Title
    major pathologic response
    Description
    the percentage of patients whose postoperative pathology showing surviving tumor cells ≤10%
    Time Frame
    Up to 2 year
    Title
    2-year overall survival rate
    Description
    the percentage of patients who survived at 2 year from the first dose
    Time Frame
    Up to 2 years
    Title
    2-year progression-free survival rate
    Description
    the percentage of patients who accepted chemoradiotherapy and survived without initial radiological progression or death from any cause at 2 year from the first dose
    Time Frame
    Up to 2 years
    Title
    2-year disease-free survival rate
    Description
    the percentage of patients who accepted surgery and survived without the first appearance of disease or death from any cause at 2 year from the first dose
    Time Frame
    Up to 2 years
    Title
    EORTC H&N 35 form evaluated quality of life
    Description
    EORTC H&N 35 form evaluated quality of life
    Time Frame
    Up to 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. a. Women of childbearing age are defined as any woman who has had menarche and has not undergone sterilization (hysterectomy or bilateral ovariectomy) and has not yet reached menopause. Menopause is defined as amenorrhea for 12 months in women> 45 without other biological or physiological causes. In addition, to confirm menopause, women under 55 must have serum follicle stimulating hormone (FSH) levels> 40 mIU / mL. Unsterilized male must be willing to take effective contraception during the study and ≥ 60 days after the last study treatment (including chemotherapy) was administered. Exclusion Criteria: 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) Controlled celiac disease Skin diseases that do not require systemic treatment (eg vitiligo, psoriasis, hair loss) Any other disease that is not expected to recur without external triggers Any active malignancy within ≤ 2 years before treatment, expect specific cancers which being studied in this study and locally recurrent cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical cancer and breast cancer in situ). Any condition requiring systemic treatment with corticosteroids (dose above 10 mg / day of prednisone or equivalent dose of similar agents) or other immunosuppressive agents within ≤ 14 days prior to treatment. Note: Patients who are currently or previously using any of the following steroid regimens can be enrolled: Adrenaline replacement (prednisone ≤10mg / day or equivalent dose of similar agents) Local, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids with minimal systemic absorption. Prophylactic short-term (≤7 days) use of corticosteroids (for example, to prevent hypersensitivity caused by contrast agent) or to treat non-autoimmune conditions (for example, delayed-type hypersensitivity reactions caused by exposure to allergens). Have a history of interstitial lung disease, non-infectious pneumonia or uncontrolled disease including pulmonary fibrosis, acute lung disease, etc. Severe chronic or active infections (including tuberculosis infections, etc.) that require systemic antibacterial, antifungal, or antiviral treatment within 14 days of treatment. History of HIV infection. Underwent any major surgery requiring general anesthesia ≤ 28 days before treatment. Previously allogeneic stem cell transplantation or organ transplantation. Have any of the following cardiovascular risk factors: Cardiogenic chest pain occurs within ≤ 28 days prior to treatment and is defined as moderate pain that limits applianceal activities of daily life. Symptomatic pulmonary embolism occurred within ≤ 28 days before treatment Acute myocardial infarction occurred within 6 months before treatment History of heart failure that has reached New York Heart Association Class III or IV ≤ 6 months before treatment. Ventricular arrhythmia of grade ≥ 2 occurred within ≤ 6 months before treatment Cerebrovascular accident occurred within ≤ 6 months before treatment Uncontrolled hypertension: SBP ≥160 mmHg or DBP ≥100 mmHg, although antihypertensive drugs were used ≤ 28 days before treatment or before the first study drug Any syncope or convulsions ≤ 28 days before treatment History of severe hypersensitivity to other monoclonal antibodies. Have received Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before the first study drug administration. Live vaccinations within ≤ 4 weeks before treatment. Note: Seasonal flu vaccines are usually inactivated vaccines and are allowed. The vaccine used in the nasal cavity is a live vaccine and is not allowed. Presence of basic medical conditions (including abnormal laboratory test values) or alcohol / drug abuse or dependence that are detrimental to study drug administration or affect drug toxicity or AE interpretation, or that may reduce compliance during the study . Participate in another therapeutic clinical trial at the same time Unintentional weight loss ≥ 5% within 1 month before treatment or severe malnutrition. Nutritional risk index (Shirasu et al 2018) can be used to determine severe malnutrition Pregnant or lactating women peripheral neuropathy ≥ grade 2 at baseline Uncontrolled diabetes, abnormalities of laboratory tests in potassium, sodium or corrected calcium>grade 1 despite standard medication,or hypoalbuminemia ≥ grade 3 within 14 days before treatment. Have received any chemotherapy, immunotherapy (eg interleukin, interferon, thymosin) or any research treatment within 14 days or 5 half-lives (whichever is longer) before the first study drug administration. Other exclusion criteria Prisoner or jailer. People who have been compulsorily detained for the treatment of a mental or physical illness, such as an infectious disease.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Chunmei Bai, doctor
    Phone
    8601069156114
    Ext
    8601069156114
    Email
    baichunmei1964@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Chunmei Bai
    Organizational Affiliation
    Peking Union Medical College Hospital
    Official's Role
    Study Chair

    12. IPD Sharing Statement

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

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