Clinical Trials /

Combination Therapy of Sintilimab and Anlotinib as a First-line Treatment in Advanced NSCLC (SUNRISE)

NCT04124731

Description:

This is an open label, multi-center, randomized control phase II trial, to compare the efficacy and safety of sintilimab combined with anlotinib versus standard platinum-based chemotherapy as a first-line treatment in advanced NSCLC patients without driven-gene mutations.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination Therapy of Sintilimab and Anlotinib as a First-line Treatment in Advanced NSCLC (SUNRISE)
  • Official Title: SUNRISE: A Phase II Randomized Control Study of Sintilimab Combined With Anlotinib Versus Standard Platinum-based Chemotherapy as a First-line Treatment in Patients With Advanced NSCLC

Clinical Trial IDs

  • ORG STUDY ID: SUNRISE
  • NCT ID: NCT04124731

Conditions

  • Carcinoma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
sintilimab plus anlotinibSintilimab plus anlotinib
ChemotherapyControl

Purpose

This is an open label, multi-center, randomized control phase II trial, to compare the efficacy and safety of sintilimab combined with anlotinib versus standard platinum-based chemotherapy as a first-line treatment in advanced NSCLC patients without driven-gene mutations.

Detailed Description

      This is an open label, multi-center, randomized control study comparing the combination of
      sintilimab and anlotinib with standard platinum-based chemotherapy in treat-naïve advanced
      (unresectable stage IIIB, IIIC and IV patients without driven-gene mutations) NSCLC patients.
      Eligible subjects are 1:1 randomized into the experimental group (sintilimab combined with
      anlotinib) or the control group (standard platinum-based chemotherapy).
    

Trial Arms

NameTypeDescriptionInterventions
Sintilimab plus anlotinibExperimentalSintilimab and anlotinib combination therapy
  • sintilimab plus anlotinib
ControlActive ComparatorStandard platinum-based chemotherapy
  • Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          1. Signed written informed consent before initiation of any study procedures

          2. Age ≥ 18 years and ≤ 75 years

          3. Histologically or cytologically confirmed NSCLC, with unresectable local advanced or
             metastatic disease (stage IIIB-IV according to NSCLC staging version 8)

          4. Epidermal Growth Factor Receptor (EGFR)/ Anaplastic Lymphoma Kinase (ALK) wild type
             non-small cell lung cancer

          5. Sufficient qualified tumor tissue or Paraffin-embedded slides are provided to detect
             the expression of PD-L1 (TPS, 22C3 antibody).

          6. At least 1 measurable disease according toRECIST 1.1

          7. None previous chemotherapy or targeted therapy. Adjuvant chemotherapy, neoadjuvant
             chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility,
             and the last treatment time must be more than 6 months before enrollment

          8. Expected survival over 3 months

          9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

         10. Brain metastasis patients with no symptoms or stable symptoms after local treatment
             are eligible, provided they meet all of the following conditions:

        1) measurable lesions outside the central nervous system 2) no central nervous system
        symptoms or no aggravation of symptoms for at least 2 weeks 3) patients who did not require
        glucocorticoid therapy or who discontinued glucocorticoid therapy within 3 days before the
        first study drug administration 11. Patients are allowed to receive palliative radiotherapy
        (including craniocerebral radiotherapy for symptomatic brain metastases) at least 1 week
        prior to enrollment and return to less than or equal to 1 degree of radiosurgery toxicity
        (CTCAE 5.0, excluding alopecia).

        12. Adequate hematologic and organ function defined by the following laboratory results
        obtained within 14 days prior to randomization: 13. For female patients of childbearing
        age, a urine or serum pregnancy test should be administered within 3 days prior to the
        first study drug administration (day 1 of cycle 1) and results should be negative. If a
        urine pregnancy test does not confirm a negative result, a blood pregnancy test is
        required. Non-childbearing female were defined as those who had been postmenopausal for at
        least 1 year or who had undergone surgical sterilization or hysterectomy.

        14. If pregnancy is potential, all patients (male and female) are required to use
        contraception with an annual failure rate of less than 1% for the entire treatment period
        up to 120 days after the last study drug administration (or 180 days after the last
        chemotherapy drug administration).

        Exclusion Criteria:

          1. Squamous cell carcinoma (including adenosquamous carcinoma); Small cell lung cancer
             (including small cell cancer and non-small cell mixed lung cancer).

          2. Patients with cavernous squamous cell carcinoma or imaging suggesting
             infiltration/invasion of large blood vessels or other high bleeding risk factors
             evaluated by the investigators.

          3. Active hemoptysis within 2 weeks before first drug administration (at least 1/2
             teaspoon blood spilt at one time);

          4. Received radiotherapy before administration of the first study drug, which met one of
             the following conditions:

        1) ≥30% of bone marrow had received radiotherapy within 14 days before treatment 2)
        received radiotherapy for lung lesions within 6 weeks before treatment with >30Gy dose
        (enrolled subjects must recover from the toxicity of previous radiotherapy to level 1 or
        below, do not need glucocorticoid treatment and have no history of radiation pneumonia) 3)
        the end time of palliative radiotherapy should be within 7 days before the first study drug
        administration 5. Major surgical treatment within 3 weeks of the first study drug
        administration (except for biopsy surgery) 6. Have Participated in other clinical studies
        or less than 4 weeks before the end of treatment in the previous clinical study 7.
        Previously diagnosis as other malignant tumors within 5 years prior to the first dose of
        study treatment, with the exception of: skin basal cell carcinoma or squamous cell
        carcinoma with radical treatment, and/or carcinoma in situ underwent radical resection 8.
        Prior treatment with PD-1 inhibitor, PD-L1 inhibitor, CTLA4 inhibitor, or anti- angiogenic
        treatment.

        9. A history of active autoimmune disease requiring systemic treatment (e.g. using drugs
        for disease remission, corticosteroids or immunosuppressor) within 2 years prior to the
        first dose of study treatment. Substitution therapy (e.g. thyroxine, insulin or
        physiological corticosteroids for treating adrenal or pituitary dysfunction) is not
        considered as a systemic treatment.

        10. Received a traditional Chinese medicine with anti-tumor effect, or an immunomodulatory
        drug (thymosin, interferon, interleukin) within 2 weeks before the first dose, or received
        major surgery within 3 weeks before the first dose 11. Systemic steroid therapy or any
        other form of immunosuppressive therapy performed within 7 days prior to the first dose of
        study (physiologic dose is allowed).

        12. The presence of clinically uncontrollable pleural effusion/peritoneal effusion 13. Have
        received a physical organ or blood system transplant 14. allergic to the active ingredients
        or excipients of the drugs studied, such as sintilimab, pemetrexed, gemcitabine,
        carboplatin, cisplatin, etc.

        15. Patients with multiple factors that affect oral medications (such as inability to
        swallow, gastrointestinal resection, chronic diarrhea, and intestinal obstruction) 16.
        Patients with bleeding tendencies (such as active gastrointestinal ulcers) or treated with
        anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; Small
        doses of warfarin (≤1mg/d), small doses of heparin (≤ 12,000 U/d) or small doses of aspirin
        (≤100mg/d) are allowed for prophylactic purposes, provided that the international
        standardized ratio of prothrombin time (INR) ≤1.5 17. Patients with severe arteriovenous
        thrombosis, such as cerebrovascular accident (including temporary ischemic attack), deep
        vein thrombosis and pulmonary embolism, which occurred within 6 months before the first
        treatment 18. Not fully recovered from toxicity and/or complications resulting from any
        intervention prior to initiation of treatment (i.e., ≤1 or baseline, excluding fatigue or
        hair loss); 19. A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2
        antibody positive) is known.

        20. Untreated active hepatitis B; 21. Active HCV-infected subjects (HCV antibody positive
        and HCV-RNA levels above the lower limit of detection) 22. Vaccination of live vaccine
        within 30 days before the first dose (1st cycle, 1st day); 23. Pregnant or lactating women
        24. Any serious or uncontrolled systemic diseases 25. Any medical history or evidence of
        disease that may interfere with the outcome of the study, or other conditions that the
        investigator considers inappropriate for the study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Respond Rate (ORR)
Time Frame:up to 24 months after enrollment or study close
Safety Issue:
Description:ORR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:up to 24 months after enrollment or study close
Safety Issue:
Description:PFS (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression)
Measure:Disease Control Rate (DCR)
Time Frame:up to 24 months after enrollment or study close
Safety Issue:
Description:DCR (per RECIST 1.1 as assessed by the investigator) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD).
Measure:Duration of Response (DoR)
Time Frame:up to 24 months after enrollment or study close
Safety Issue:
Description:DoR (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) until the date for the first documented response of progressive disease (PD) or death in the absence of progression.
Measure:Overall Survival (OS)
Time Frame:up to 24 months after enrollment or study close
Safety Issue:
Description:OS (per RECIST 1.1 as assessed by the investigator) is defined as the time from the date of randomisation until death due to any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shanghai Chest Hospital

Trial Keywords

  • Advanced
  • Non-Small Cell Lung Cancer
  • Sintilimab
  • PD-1
  • Anlotinib
  • Anti-angiogenisis

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