Clinical Trials /

Sintilimab in FH-deficient Renal Cell Carcinoma

NCT04146831

Description:

This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma.

Related Conditions:
  • Renal Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sintilimab in FH-deficient Renal Cell Carcinoma
  • Official Title: Phase II Study of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: CIBI30820191025
  • NCT ID: NCT04146831

Conditions

  • Renal Cell Carcinoma
  • FH-deficient
  • Sintilimab

Interventions

DrugSynonymsArms
SintilimabSintilimab

Purpose

This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma.

Detailed Description

      Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of RCC
      characterized by germline/somatic mutation of the fumarate hydratase (FH) gene, and is an
      extremely aggressive tumor, with a propensity to disseminate early even in the setting of a
      small primary tumor.

      Loss-of-function mutation of FH results in the accumulation of fumarate, impairment of
      oxidative phosphorylation, alteration of the metabolic state, and stabilization of
      hypoxia-inducible factor (HIF)-1α, thus activating angiogenic and oxidative stress response
      pathways. Unlike the robust response of clear cell RCC (ccRCC) to antiangiogenic agents,
      blocking the antiangiogenic pathway does not lead to better outcomes in FH-deficient RCC.
      Anti-mTOR agents are also ineffective.

      Although the National Comprehensive Cancer Network (NCCN) guideline recommends the
      combination of bevacizumab plus erlotinib or everolimus for metastatic FH-deficient RCC,
      high-level evidence for standardized systematic therapy remains scarce.

      In the present study, the investigators plan to assess the efficacy and safety of
      immunotherapy with Sintilimab as second-line treatment in FH-deficient RCC, and to explore
      potential biomarkers related to the treatment efficacy by means of detection, including but
      not limited to the next-generation sequencing, flow cytometry, etc.
    

Trial Arms

NameTypeDescriptionInterventions
SintilimabExperimentalSintilimab is administered in this arm.
  • Sintilimab

Eligibility Criteria

        Inclusion Criteria:

          1. ≥18 years old;

          2. histopathological evidence of FH-deficient renal cell carcinoma, which was confirmed
             by Sanger or next-generation sequencing after initial screening by IHC.

          3. included patients must be diagnosed with metastatic renal cell carcinoma or have a TNM
             stage IV (according to 2009 TNM Classification). Patients must have received treatment
             of targeted agents or immunotherapy (including cytokine therapy) before enrollment.

          4. ECOG score ≤2;

          5. life expectancy ≥ 3 months;

          6. sign informed consent, and be able to follow the visit and related procedures
             stipulated in the program;

          7. agree to collect tumor tissue, blood and other specimens required by this study and
             apply them to relevant studies;

          8. important organs and bone marrow functions meet the following requirements: absolute
             neutrophil count (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin (HGB)
             ≥9g/dL;Liver function: serum total bilirubin (TBIL) ≤1.5 times normal upper limit
             (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5
             times ULN, serum albumin (ALB) ≥ 2.8g /dL. Renal function: serum creatinine (Cr)
             ≤1.5×ULN, or creatinine clearance ≥40 mL/min

        Exclusion Criteria:

          1. patients with other malignant tumors with different primary sites or histology from
             the tumor evaluated in this study within 2 years of personal history, except those
             with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or cervical
             carcinoma in situ under good control;

          2. major surgery or severe trauma within 4 weeks before enrollment;

          3. immunosuppressive drugs were used within 4 weeks prior to the first dose of study
             therapy, excluding local glucocorticoids, inhaled or otherwise, or systemic
             glucocorticoids at physiological doses (i.e., no more than 10mg/ d prednisone or
             equivalent doses of other glucocorticoids);

          4. known or suspected active autoimmune diseases (congenital or acquired), such as
             interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation,
             vasculitis, nephritis, thyroiditis, etc. Patients with type 1 diabetes with good
             insulin control can also be enrolled.

          5. known allogeneic organ transplantation (except corneal transplantation) or allogeneic
             hematopoietic stem cell transplantation;

          6. allergic to any component of monoclonal antibody;

          7. suffering from other uncontrolled serious diseases, including but not limited to: A)
             severe infection in the active phase or clinically poorly controlled; B) HIV infection
             (HIV antibody positive); C) acute or chronic active hepatitis b (HBsAg positive and
             HBV DNA>1*103/ml) or acute or chronic active hepatitis c (HCV antibody positive and
             HCV RNA>15IU/ml); D) active tuberculosis, etc.;

          8. class iii-iv congestive heart failure (New York heart association classification),
             poorly controlled and clinically significant arrhythmia;

          9. uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic
             blood pressure ≥100mmHg);

         10. had any arterial thrombosis, embolism or ischemia, such as myocardial infarction,
             unstable angina, cerebrovascular accident or transient ischemic attack, etc. within 6
             months before the selected treatment;

         11. diseases requiring the use of warfarin (coumarin) for anticoagulant treatment;

         12. uncontrolled hypercalcemia (more than 1.5 mmol/L of calcium or calcium greater than 12
             mg/dL or adjusted serum calcium greater than ULN), or symptomatic hypercalcemia
             requiring continued bisphosphate treatment;

         13. accompanied by other malignant tumors (except those that have been cured, such as
             cervical carcinoma in situ, non-melanoma skin cancer, etc.);

         14. other acute or chronic diseases, psychiatric disorders, or laboratory abnormalities
             that may result in increased risk associated with study participation or study drug
             administration, or interference with the interpretation of study results, and
             ineligibility to participate in the study as determined by the investigator;

         15. pregnant or lactating women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:6-month PFS rate (6 month progression-free survival rate)
Time Frame:Up to 24 months
Safety Issue:
Description:Disease progression was defined as the time from first administration of Sintilimab to progression of disease (PD) or death, according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description:Complete response (CR) or partial response (PR) by Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
Measure:Duration of response (DOR)
Time Frame:Up to 24 months
Safety Issue:
Description:DOR is defined as the time from the date of first remission to the date of disease progression or death.
Measure:Progression-free survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:PFS is defined as the time from first administration of Sintilimab to the date of disease progression or death according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
Measure:Overall survival (OS)
Time Frame:Up to 24 months
Safety Issue:
Description:OS is defined as the time from first administration of Sintilimab to the date of death according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
Measure:Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (FKSI-19)
Time Frame:Up to 24 months
Safety Issue:
Description:FKSI-19 score change over time from baseline to disease progression. The scale of FKSI-19 is from 0 to 48, and higher scores indicate worse quality of life.
Measure:Functional Assessment of Cancer Therapy- Kidney Symptom Index- Disease related Symptoms (FKSI-DRS)
Time Frame:Up to 24 months
Safety Issue:
Description:FKSI-DRS score change over time from baseline to disease progression. The scale of FKSI-DRS is from 0-36, and higher scores indicate worse quality of life.
Measure:EuroQol five-dimension scale (EQ-5D)
Time Frame:Up to 24 months
Safety Issue:
Description:EQ-5D-5L score change over time from baseline to disease progression. The EQ-5D-5L is consisted of five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Higher scores indicate poorer health.
Measure:Visual analogue scale (VAS)
Time Frame:Up to 24 months
Safety Issue:
Description:VAS pain score change over time from baseline to disease progression. The scale of VAS is from 0-10, and higher scores indicate worse symptom of pain.
Measure:Frequency of treatment-related adverse events (AEs)
Time Frame:Up to 24 months
Safety Issue:
Description:Records were made according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:West China Hospital

Trial Keywords

  • FH-deficient
  • Sintilimab
  • Second-line

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