Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma

April 7, 2024 updated by: Hao Zeng, West China Hospital

Single-arm Phase II Clinical Trial to Evaluate the Initial Efficacy and Safety of Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma

This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab injection combined with Inlyta in fumarate hydratase-deficient renal cell carcinoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Our previous genetic research as well as other published data indicated the possible well response to combination of immunotherapy with targeted therapy in FH-deficient renal cell carcinoma, therefore the investigators intented to perform this single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab injection combined with Inlyta in FH-deficient renal cell carcinoma.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • West China Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18, no gender limitation;
  2. Histopathological confirmed RCC, and diagnosed as FH-dRCC by Sanger or NGS sequencing after being included in preliminary IHC screening;
  3. The patients incuded must be diagnosed with metastatic RCC or TNM stage IV (according to the 2009 TNM staging system), with distant metastasis confirmed by radiology or pathology.
  4. Have not received systemic treatment, including cytokines, targeted drugs, or other experimental drugs, or have received targeted drugs (within the range of 1st-line targeted drugs recommended by NCCN2022 for renal cancer) with single drug treatment for less than 1 month and have completed the washout period. ECOG score ≤ 2;
  5. Life expectancy ≥ 3 months;
  6. Signed written informed consent form and willing and able to comply with scheduled visits and other requirements of the study；
  7. Agree to collect tumor tissue and blood samples required for this study and apply the samples to relevant studies;
  8. Adequate organ and bone marrow function: absolute neutrophil count (ANC): ≥1×109/L, platelet count (PLT) ≥50×109/L, hemoglobin content (HGB) ≥80g/L; Liver function: total bilirubin (TBIL) ≤3×normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5×ULN, albumin ≥20g/L; Renal function: serum creatinine (Cr) ≤3×ULN.

Exclusion Criteria:

  1. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 antibody, or any other antibodies or drugs specifically targeting co-stimulatory or checkpoint pathways of T cells;
  2. Active brain metastasis;
  3. Other malignancy with primary site or histological type different from tumors evaluated in this study within 2 years of personal history, except skin basal cell carcinoma, squamous cell carcinoma or adequately treated cervical carcinoma in situ;
  4. Underwent major operation (craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study medication or with severe trauma;
  5. Received systemic treatment with corticosteroids (> 10mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
  6. Known or suspected active autoimmune disease (congenital or acquired), including interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. Patients with type I diabetes, hypothyroidism that only requires systemic treatment (including vitiligo, psoriasis, alopecia, etc.), or conditions that are not expected to recur in the absence of external triggers are eligible to participate in this study; Known history of allogeneic organ (except corneal transplantation) or allogeneic hemopoietic stem cell transplantation;
  7. Known allergy or hypersensitivity to any monoclonal antibodies or any components used in their preparation;

  8. Uncontrolled concomitant disease, including but not limited to:

    1. Active or poorly controlled severe infection;
    2. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
    3. Known acute or chronic active hepatitis B infection (HBsAg positive and HBV DNA>1*103/ml), or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA>15IU/ml);
    4. Active tuberculosis;
  9. Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia;
  10. Poorly controlled arterial hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) with standard treatment;
  11. Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack, within 6 months of enrollment;
  12. Diseases that require anticoagulant treatment with warfarin (coumarin);
  13. Poorly controlled hypercalcemia (Ca2+ > 1.5mmol/L, or serum calcium > 12mg/dL, or corrected serum calcium > ULN), or symptomatic hypercalcemia requiring bisphosphate treatment;
  14. Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study;
  15. Women who are pregnant or nursing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sintilimab injection combined with Inlyta

Sintilimab injection 10ml: 100mg, 200mg intravenously, once every three weeks. Course of treatment: discontinue medication when the disease progresses clinically or radiologically.

Inlyta 5mg orally, twice a day. Course of treatment: continue treatment as long as a clinical benefit is observed, or until an unacceptable toxicity is present that cannot be controlled by combination or dose adjustment.

In the whole research process, if the disease progresses, the attending doctor has the right to carefully choose other anti-tumor methods, including radiotherapy, chemotherapy and other targeted drugs.
Drug: Sintilimab injection plus Inlyta treatment
Combined Sintilimab injection and Inlyta treatment in FH-deficient RCC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: 3 years
objective response rate
3 years
PFS
Time Frame: 3 years
progression-free survival
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: 3 years
overall survival
3 years
EQ-5D-5L
Time Frame: Up to 36 months
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.
Up to 36 months
FKSI-19
Time Frame: Up to 36 months
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.
Up to 36 months
DCR
Time Frame: 3 years
Disease control rate
3 years
Duration of response
Time Frame: 3 years
time from the first occurrence of treatment response (CR or PR) to disease progression or death
3 years
VAS
Time Frame: 3 years
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.
3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Investigators

  • Principal Investigator: Hao Zeng, West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

August 15, 2019

First Submitted That Met QC Criteria

May 9, 2020

First Posted (Actual)

May 14, 2020

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 7, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20190813

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

There is a plan to make IPD and related data dictionaries available.

IPD Sharing Time Frame

Data would be available starting from the time when summary data are published or otherwise made available, for 3 years.

IPD Sharing Access Criteria

Other researchers access the data by sending an email to our PI.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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