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Anrotenib Plus Toripalimab Versus Toripalimab in Patients With Advanced Esophageal Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT04229849
Recruitment Status : Not yet recruiting
First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Henan Cancer Hospital

Tracking Information
First Submitted Date  ICMJE January 13, 2020
First Posted Date  ICMJE January 18, 2020
Last Update Posted Date January 18, 2020
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
Overall Survival (OS) [ Time Frame: up to 2 years ]
From the first day of treatment to death or last survival confirm date
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
  • Progression-free Survival (PFS) [ Time Frame: up to 2 years ]
    From the first day of treatment until the date of first documented progression or date of death from any cause
  • Objective Response Rate (ORR) [ Time Frame: up to 2 years ]
    To compare objective response rate of the two arms from date of anti-cancer therapy until progression
  • Disease Control Rate (DCR) [ Time Frame: up to 2 years ]
    To compare disease control rate of the two arms from date of anti-cancer therapy until progression
  • Number of Participants with Treatment-related Adverse Events Treatment-related adverse events [ Time Frame: up to 2 years ]
    Number of Participants with Treatment-related Adverse Events Treatment-related adverse events will be assessed by NCI CT CAE v5.0
  • Assessment of Health-related quality of life [ Time Frame: up to 2 years ]
    Quality of Life Questionnaire (QLQ-C30) will be evaluated since treatment begins. At the end of the trail, the differences between the two indicators will be compared with Mixed-effects model repeated measures (MMRM), where the baseline is scored as a covariant and the treatment group as a fixed variable. In addition, the baseline values of the two scores, the value of each visit, and the change value of the baseline will be statistically described.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anrotenib Plus Toripalimab Versus Toripalimab in Patients With Advanced Esophageal Squamous Cell Carcinoma
Official Title  ICMJE A Randomized, Open-label, Controlled, Multicenter Phase II Trial of Anrotenib Plus Toripalimab Versus Toripalimab for Following Treatment of Advanced Esophageal Squamous Cell Carcinoma After Chemotherapy Failure
Brief Summary The aim of this study is to investigate the efficacy and safety of anrotenib plus toripalimab in the treatment of advanced esophageal squamous cell carcinoma. In addition, the investigators will explore the possible mechanisms of anrotinib combined with toripalimab in advanced esophageal squamous cell carcinoma, and screen out biomarkers that can predict the efficacy of combination therapy.
Detailed Description There is no standard recommendation for the treatment of advanced esophageal squamous cell cancer after chemotherapy failure. Anrotinib combined with triplizumab have showed synergistic effect in the tumor treatment, and they have demonstrated robust antitumor activity in the first-line treatment of advanced NSCLC with negative driving gene. However, there is no related report on the efficacy in the treatment of advanced esophageal squamous cell carcinoma. The aim of this study is to investigate the efficacy and safety of anrotenib plus toripalimab in the treatment of advanced esophageal squamous cell carcinoma. In addition, the investigators will explore the possible mechanisms of anrotinib combined with toripalimab in advanced esophageal squamous cell carcinoma, and screen out biomarkers that can predict the efficacy of combination therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Squamous Cell Carcinoma
Intervention  ICMJE
  • Drug: Anrotenib plus Toripalimab
    Anrotenib: 10 mg on day 1-14 orally repeated every 21 days; Toripalimab: 240 mg on day 1 intravenously repeated every 21 days.
    Other Name: FOCUS V
  • Drug: Toripalimab
    Toripalimab: 240 mg on day 1 intravenously repeated every 21 days.
Study Arms  ICMJE
  • Experimental: Anrotenib plus Toripalimab
    Anrotenib: 10 mg on day 1-14 orally repeated every 21 days; Toripalimab: 240 mg on day 1 intravenously repeated every 21 days; Until disease progression according to the RECIST 1.1 and irRECIST standard, intolerance of toxicity, withdrawal of informed consent from the subject, or tripleuriumab administration up to 2 years.
    Intervention: Drug: Anrotenib plus Toripalimab
  • Active Comparator: Toripalimab
    Toripalimab: 240 mg on day 1 intravenously repeated every 21 days; Until disease progression according to the RECIST 1.1 and irRECIST standard, intolerance of toxicity, withdrawal of informed consent from the subject, or tripleuriumab administration up to 2 years.
    Intervention: Drug: Toripalimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 13, 2020)
164
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Confirmed esophageal squamous cell carcinoma patients by histopathological or cytopathological examinations.
  • 2. Advanced esophageal squamous cell carcinoma patients with progression after chemotherapy of taxol and/or platinum or fluorouracil.
  • 3. According to the evaluation criteria of solid tumor efficacy (RESIST 1.1), there should be at least one measurable lesion (empty organs such as esophagus and stomach cannot be taken as the measurable lesion), and the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area is also selected as the target lesion if the lesion progression is confirmed).
  • 4. A histological specimen can be provided for secondary testing.
  • 5. ≥18 years old, male or female.
  • 6. ECOG performance status 0-1.
  • 7. Life expectancy ≥ 12 weeks.
  • 8. The main organ function meets the following criteria within 7 days before treatment:

    1. Blood routine examination criteria (without blood transfusion within 14 days): hemoglobin (HB) ≥ 90g/L, the absolute value of neutrophils (ANC) ≥ 1.5 x 10^9/L, platelet (PLT) ≥ 80 x 10^9/L.
    2. Biochemical examinations must meet the following criteria: total bilirubin (TBIL) ≤ 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN, serum creatinine (Cr) ≤ 1.5 x ULN or creatinine clearance (CCR) ≥ 60 mL/min.
    3. Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%).
  • 9. Fertile men and women must use effective contraception during the study period and within 6 months after the end of the study.
  • 10. The patient volunteered to participate in the study and signed an informed consent form.

Exclusion Criteria:

  • 1.Patients exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in site, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumor), Tis (in situ carcinoma), and T1 (tumor infiltrating basement membrane)); Patients with rapid progress within 3 months.
  • 2. History of gastrointestinal perforation and/or fistula within 6 months prior to the first administration.
  • 3. Esophageal lesion obviously invading the adjacent organs (major arteries or trachea), resulting in a higher risk of bleeding or fistula.
  • 4. Received any of the following treatment:

    1. Previous treatment with anti-PD-1 antibodies or anti-PD-L1 antibodies;
    2. Received any experimental drug within 4 weeks prior to the first administration of the study drug;
    3. Enroll in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up;
    4. Receive the last dose of anticancer therapy (including radiotherapy, etc.) within 4 weeks before the first administration of the study drug;
    5. Patients who need to be given corticosteroids (the equivalent dose of > 10 mg prednisone per day) or other immunosuppressants for systemic treatment within 2 weeks prior to the first use of the study drug, except the use of corticosteroids for esophageal local inflammation and the prevention of allergies, nausea and vomiting. In the absence of active autoimmune disease, inhaled or topical corticosteroid of an equivalent dose of > 10mg prednisone per day is permitted;
    6. Received an anti-tumor vaccine or received a live vaccine within 4 weeks prior to the first administration of the study drug
    7. Received major surgery or severe trauma within 4 weeks prior to first administration of the study drug.
  • 5. History of immunodeficiency disease, including HIV positive and other acquired or congenital immunodeficiency diseases, or history of organ transplantation allogeneic bone marrow transplantation.
  • 6. Toxicity of previous antitumor treatment did not return to the level ≤NCI CTC AE V5.0 grade 1 (except alopecia) or to the level specified in the inclusion/exclusion criteria.
  • 7. History of allergy to monoclonal antibody or the ingredients of the study drug.
  • 8. Significantly malnourished patients. Exclusion is performed if the patient is receiving intravenous fluids or is required to be hospitalized for continuous infusion therapy. Patients with good nutrition control ≥ 28 days can be enrolled before randomization.
  • 9. Any severe and/or uncontrolled disease, including:

    1. Patients with hypertension whose blood pressure can't be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg);
    2. Grade 1 or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480 ms) or grade 2 and above congestive heart failure according to New York Heart Association (MYHA) classification;
    3. Severe or uncontrolled disease or active infection (≥ NCI CTC AE V5.0 grade 2), which the investigators believe may increase the risk associated with patient participation and drug administration;
    4. Renal failure requiring hemodialysis or peritoneal dialysis;
    5. Patients of diabetes who have poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L);
    6. Urine routine showed urinary protein ≥ 2 + and 24-hour urine protein quantitation > 1.0 g;
    7. Patients of seizures requiring treatment.
  • 10. Any bleeding event ≥ NCI CTC AE V5.0 grade 3 or unhealed wounds, ulcers or fractures in 4 weeks prior to enrollment.
  • 11. Arterial/venous thrombosis events within 3 months, such as cerebrovascular accidents (including transient ischemic attacks), deep venous thrombosis and pulmonary embolism.
  • 12. Active autoimmune diseases or the history of autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Except patients with vitiligo or childhood asthma/allergies that have been cured and do not require any intervention as adults, autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone, type 1 diabetes using a steady dose of insulin.
  • 13. History of interstitial pulmonary disease (excluding radiation pneumonia without hormone therapy) and non-infectious pneumonia.
  • 14. Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year prior to enrollment but without formal treatment.
  • 15. Patients with active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10^4 copies/mL) and hepatitis C (HCV-RNA higher than the lower limit of the assay).
  • 16. Patients may have other factors that cause them to be forced to terminate the study, such as other serious diseases (including mental illness) that require combined treatment, serious abnormalities in laboratory test, and family or social factors, which may affect the safety of patients or the collection of experimental data.
  • 17. Patients with brain metastases.
  • 18. Woman who is pregnant or nursing.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ying Liu 13783604602 yaya7207@126.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04229849
Other Study ID Numbers  ICMJE HNCH-GI-006
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Henan Cancer Hospital
Study Sponsor  ICMJE Henan Cancer Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Baoxia He Henan Cancer Hospital/The affiliated Cancer Hospital of Zhengzhou University
PRS Account Henan Cancer Hospital
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP