Clinical Trials /

Assessing Safety and Efficacy of Sintilimab and Metformin Combination Therapy in SCLC

NCT03994744

Description:

In this Single arm study, histologically or cytologically confirmed ED-stage small cell lung cancer (SCLC) patients resistant to or relapsed after standard chemotherapy will be enrolled to investigate the Efficacy and Safety of a Combination of Sintilimab and Metformin. Primary outcome: Objective response rate (ORR), Safety of the combination therapy Secondary outcome: Overall survival (OS), Progression-free survival (PFS), Duration of response(DOR),

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Assessing Safety and Efficacy of Sintilimab and Metformin Combination Therapy in SCLC
  • Official Title: A Phase II Open-label, Single-arm Study Assessing the Efficacy and Safety of Combination Therapy of Sintilimab and Metformin With Relapsed PD-L1 Positive Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: HNCH-SCLC-2019260
  • NCT ID: NCT03994744

Conditions

  • Small-cell Lung Cancer
  • Small Cell Lung Carcinoma
  • Small Cell Lung Cancer Recurrent
  • Small Cell Lung Cancer Extensive Stage

Interventions

DrugSynonymsArms
PD-1 inhibitorSintilimab, IBI380Sintilimab and Metformin
MetforminSintilimab and Metformin

Purpose

In this Single arm study, histologically or cytologically confirmed ED-stage small cell lung cancer (SCLC) patients resistant to or relapsed after standard chemotherapy will be enrolled to investigate the Efficacy and Safety of a Combination of Sintilimab and Metformin. Primary outcome: Objective response rate (ORR), Safety of the combination therapy Secondary outcome: Overall survival (OS), Progression-free survival (PFS), Duration of response(DOR),

Detailed Description

      Exploratory Endpoints:

      The association between the efficacy of the combination treatment and changes in CTC counts
      after administration of the treatment.

      Evaluating the correlation between programmed death ligand 1 (PD-L1) expression derived from
      circulating tumor cells (CTC) and tumor tissue cells, and the predictive role of CTC PD-L1
      expression in ED-SCLC.

      The compositional changes in the gut microbiota after administration of the treatment and its
      association with the efficacy of the combination treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Sintilimab and MetforminExperimentalParticipants will be given intravenous administration of Sintilimab (1200mg/3w) Metformin treatment will be given (day20) 1 week before the second administration of Sintilimab a a dose of 2000 mg daily (1000mg BID). The duration of treatment will be up to one year, or till the disease progression, death, or unacceptable toxicity show up.
  • PD-1 inhibitor
  • Metformin

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patient, age≥18 and≤65;

          2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;

          3. The life expectancy of greater than 12 weeks;

          4. Participants must have histologically or cytologically confirmed metastatic or
             extended disease of SCLC (ED-SCLC).

          5. According to RECIST1.1, participants must have been confirmed Disease progression
             (within 6 months, confirmed by imaging test)after platinum-based doublet chemotherapy
             OR after (PFS>6 months, ) platinum-based doublet chemotherapy and refused to continue
             chemotherapy, OR after second-line or more lines of systemic chemotherapy limited
             disease SCLC (LD-SCLC) patients with disease progression after Synchronous
             chemoradiotherapy, must receive firstline systematic platinum-based doublet
             chemotherapy and refused to receive chemotherapy again.

          6. Evaluable or measurable lesion is required, defined as at least one lesion (not brain
             metastasis) that can be accurately measured based on RECIST 1.1;

          7. Participant need to provided tumor tissue (from an archival tumor sample obtained
             within 1 year or from a new biopsy sample) for PD-L1 immunohistochemical (IHC) assay,
             and PD-L1expression in more than 1% cells is required;

          8. Participant is able to the ability to swallow oral medications

          9. Participants have to meet the following criteria to ensure function of vital organs:

             Absolute neutrophil count (ANC) ≥1.5×109/L or White blood cell count
             >3.5×109/L;Platelets >80×109/L; Hemoglobin (HGB)≥90 g/L;Serum total bilirubin ≤ 1.5 x
             upper limit of normal (ULN); AST(SGOT)/ALT(SGPT) ≤2.5 ×ULN; ALB≥2.8g/dL;Serum
             creatinine ≤ 1.5 x institutional ULN OR creatinine clearance ≥40 mL/min using the
             Cockcroft-Gault equation

         10. Participants must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) through the treatment, and for at least 180 days after the
             last dose of study treatment; Participants must have the ability to understand and be
             willing to sign a written informed consent document.

        Exclusion Criteria:

          1. Participants who were diagnosed as mixed pathological type of small cell lung cancer

          2. Participants who had long-term use of metformin (>2 weeks) 6 months prior to study
             entry, or diagnosed with type-2 diabetes,

          3. Participants received treatment with anti-PD1, -PDL1, -CTLA4, -CD137 inhibitors
             before, or any therapy specifically targeting T-cell co-stimulation or checkpoint
             pathways.

          4. Participants received cellular immunotherapy before

          5. Participants with Uncontrolled intercurrent illness including, but not limited to:

             Ongoing or active infection; Known history of Human Immunodeficiency Virus (HIV)
             infection Acute or chronic active hepatitis B (HBV DNA >1*10^3 copies/ml or >200
             IU/mL) or, acute or chronic active hepatitis C (with a positive Hepatitis C antibody
             test result) Active tuberculosis Congestive heart failure (Class III-IV, according to
             New York Heart Association classification), or and clinically significant Cardiac
             arrhythmia if poorly controlled; Uncontrolled arterial hypertension (systolic blood
             pressure ≥160mmHg or diastolic blood pressure ≥100mmHg) Any arterial thrombosis,
             embolism, ischemia, myocardial infarction, unstable angina, or cerebrovascular
             accident within 6 months prior to enrollment,

          6. Participants with symptomatic Central nervous metastasis or meningeal carcinomatosis
             are excluded; Participants with asymptomatic brain metastases or with brain metastases
             that have been treated and stable in a subsequent scan are allowed to include if there
             is measurable lesion outside the Central nervous system and no history of intracranial
             hemorrhage, and not midbrain, pons, cerebellum, medulla or spinal cord metastasis, and
             do not need glucocorticoid therapy.

          7. Participants receiving glucocorticoid (>30 mg prednisone equivalent a day) or any
             Immunosuppressive drug within 14 days prior to study recruitment; Participants
             receiving inhaled or Topical corticosteroids, adrenal corticosteroid replacement
             therapy (>10 mg prednisone equivalent a day) are allowed if they have no active
             autoimmune disease

          8. Participants with a known additional malignancy (Except for Non-melanoma skin cancer
             and the following in situ carcinoma: in situ bladder carcinoma, in situ gastric
             carcinoma, in situ colonic carcinoma, in situ endometrial carcinoma, in situ cervical
             carcinoma /dysplasia, in situ melanoma carcinoma and in situ breast Carcinoma) unless
             they Maintained Complete Remission for at least 5 years and do not need corresponding
             treatment during the study

          9. Participants who have not recovered (i.e., ≤ Grade 1 according to NCI CTCAE V4or at
             baseline) from adverse effects due to a previously administered agent.

         10. Participants who have uncontrollable effusion, such as pleural and ascites that cannot
             be controlled by drainage or other treatment

         11. Patients who have active autoimmune diseases; excluding patients whose active
             autoimmune disease is caused by Vitiligo or asthma that is completely relieved in
             childhood and Patients with hypothyroidism requiring only hormone replacement therapy

         12. Patients with known Allogeneic organ transplantation (except corneal transplantation)
             or allogeneic hematopoietic stem cell transplantation

         13. Patients who are pregnant or breastfeeding,

         14. Patients who are allergic to monoclonal antibody drugs

         15. Patients who have contraindications to metformin including severe allergic reactions
             and intolerance

         16. Patients who are not eligible for this study, as Assessed by Investigator
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate of Sintilimab and Metformin(ORR)
Time Frame:1 year
Safety Issue:
Description:Assessing the response of treatment of each patient using RECIST 1.1 criteria, the investigators calculate the percentage of patients meet partial response (30% decrease in diameter) and complete response in the arm.

Secondary Outcome Measures

Measure:Median overall survival (OS) time of Sintilimab and Metformin
Time Frame:2 years
Safety Issue:
Description:Use K-M to estimate the median OS of single arm.
Measure:Median progression free survival(PFS) of Sintilimab and Metformin
Time Frame:1 year
Safety Issue:
Description:Use K-M to estimate the median PFS of single arm.
Measure:Median duration of response (DoR) of Sintilimab and Metformin
Time Frame:1 year
Safety Issue:
Description:Use K-M to estimate the median DoR of single arm.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hunan Cancer Hospital

Trial Keywords

  • immunotherapy
  • metformin
  • PD-L1
  • PD-1 checkpoint inhibitor

Last Updated

August 22, 2019