Vorolanib Plus Sintilimab for Advanced Renal Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitors Based Combination Therapy

July 25, 2024 updated by: Hao Zeng

A Prospective, Multicenter, Phase II Clinical Trial of Vorolanib in Combination With Sintilimab for Advanced Renal Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitors Based Combination Therapy

This Phase II trial assesses Vorolanib and Sintilimab for advanced renal cell carcinoma after previous therapy failure. Participants receive the treatment until disease progression, intolerable side effects, death, or withdrawal. The primary endpoint is progression-free survival (PFS).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase II, multicenter, single-arm clinical trial designed to assess the efficacy and safety of Vorolanib in combination with Sintilimab in treating advanced renal cell carcinoma following the failure of prior immune checkpoint inhibitors based combination therapy. Participants will continue to receive Vorolanib and Sintilimab until disease progression, development of unacceptable toxic effects, death, or if the physician or patient decides to withdraw from the study. The primary endpoint is progression-free survival (PFS) according to RECIST v1.1 criteria as evaluated by the investigators.

Study Type

Interventional

Enrollment (Estimated)

67

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 Contact

Study Locations

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

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years and ≤75 years, any gender.
  2. Histologically confirmed diagnosis of renal cell carcinoma.
  3. Diagnosis of metastatic renal cell carcinoma or TNM stage IV (according to the 2017 TNM staging system). Evidence of distant metastasis by imaging or pathology.
  4. Prior immune checkpoint inhibitors based combination therapy, dual immune combination, or immune monotherapy with disease progression, or who have received second/third line targeted monotherapy, immune monotherapy, or a change in immune-based combination therapy after failure of one of the above therapies for no more than 1 month and have completed the washout period. ECOG performance status ≤2.
  5. Life expectancy of at least 3 months.
  6. Signed informed consent and ability to comply with the protocol-specified visits and procedures.
  7. Agreement to provide tumor tissue and blood specimens required for the study.
  8. Adequate organ and bone marrow function as follows: absolute neutrophil count (ANC) ≥1×10^9/L, platelets (PLT) ≥50×10^9/L, hemoglobin (HGB) ≥80g/L; liver function: serum total bilirubin (TBIL) ≤3 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5 times ULN, serum albumin (ALB) ≥20 g/L; renal function: serum creatinine (Cr) ≤3×ULN.

Exclusion Criteria:

  1. Pathologically diagnosed with non-renal cell carcinoma, collecting duct carcinoma.
  2. First-line treatment with targeted monotherapy, or progression after first-line immune checkpoint inhibitors based combination therapy, followed by more than 1 month of treatment with targeted therapies, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies specifically targeting T cell co-stimulation or checkpoint pathways and/or incomplete washout period.
  3. Active brain metastases.
  4. Personal history of other malignant tumors within 3 years with a different primary site or histology than that being evaluated in this study, excluding patients with well-controlled basal cell carcinoma, squamous cell carcinoma, or cervical intraepithelial neoplasia.
  5. Major surgery or severe trauma within 4 weeks prior to enrollment.
  6. Subjects with conditions requiring systemic corticosteroids (>10mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days prior to initial study drug administration. Subjects with inactive autoimmune disease are allowed to receive local, ophthalmic, intra-articular, intranasal, inhaled corticosteroids, or adrenal replacement steroids (>10mg/day prednisone dose or equivalent).
  7. Known or suspected active autoimmune disease (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. Subjects with type 1 diabetes, thyroid dysfunction requiring only hormone replacement therapy, skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment, or conditions expected not to recur in the absence of external triggering factors are allowed to participate in this study. Known allogeneic organ transplant (excluding corneal transplant) or allogeneic hematopoietic stem cell transplant.
  8. Allergy to any component of monoclonal antibodies.

  9. Uncontrolled other severe diseases, including but not limited to:

    1. Severe infection in the active or poorly controlled clinical phase;
    2. HIV infection (HIV antibody positive);
    3. 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);
    4. Active pulmonary tuberculosis, etc.
  10. NYHA class III-IV congestive heart failure, persistent symptomatic arrhythmia, uncontrolled atrial fibrillation; multiple echocardiographic assessments of left ventricular ejection fraction (LVEF) lower than the lower limit of normal.
  11. Uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg);
  12. Any arterial thrombosis, embolism, or ischemia in the past 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, etc.;
  13. Diseases requiring warfarin (coumarin) anticoagulant therapy;
  14. Uncontrolled hypercalcemia (calcium ion >1.5 mmol/L or calcium >12 mg/dL or corrected serum calcium >ULN), or symptomatic hypercalcemia requiring continued bisphosphonate therapy;
  15. Uncontrolled adrenal insufficiency;
  16. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months;
  17. Severe, non-healing wounds or ulcers;
  18. Gastrointestinal diseases with impaired gastrointestinal function (such as malabsorption, ulcerative disease, uncontrollable nausea, vomiting, diarrhea, or small bowel resection);
  19. Other acute or chronic diseases, mental illnesses, or laboratory abnormalities that may lead to the following outcomes: increased risk associated with study participation or drug administration, or interference with interpretation of study results, and deemed ineligible for study participation at the discretion of the investigator;
  20. Pregnant or lactating women.

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: Combination treatment group
Participants in this group will receive vorolanib tablets, 200 mg orally once daily, plus sintilimab injection, 200 mg intravenously every three weeks.
Drug: Vorolanib Tablets
Multi-targeted receptor tyrosine kinase inhibitor with potent inhibition of VEGFR2, KIT, PDGFR, FLT3 and RET, exerting anti-tumor effects mainly through inhibition of neovascularization.
Other Names:
  • Vorolanib
Drug: Sintilimab Injection
Recombinant human-derived immunoglobulin G (IgG4)-type anti-programmed cell death receptor-1 (PD-1) monoclonal antibody, by binding to PD-1 and blocking PD-1 binding to PD-L1 and PD-L2, disarms the immunosuppressive effect, activates T-cell function, and enhances T-cell immunosurveillance and killing ability against tumors to generate tumor immune response.
Other Names:
  • Sintilimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 3 years
Progression-free survival is assessed by investigators based on RECIST1.1, including disease progression or death from any cause.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 3 years
Objective response rate is the proportion of participates with complete response (CR) or partial response (PR), based on RECIST1.1.
3 years
Overall Survival (OS)
Time Frame: 3 years
Overall survival is the time from starting treatment to still being alive.
3 years
Adverse Events (AEs)
Time Frame: 3 years
Adverse events are the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0, including type and severity.
3 years
Disease Control Rate (DCR)
Time Frame: 3 years
Disease control rate is the proportion of participates with complete response (CR), partial response (PR) or stable disease (SD), based on RECIST1.1.
3 years
Duration of Response (DoR)
Time Frame: 3 years
Duration of response is the time from first response (complete or partial response) to disease progression or death.
3 years
Quality of Life (QoL) assessed by FKSI-19
Time Frame: 3 years
Quality of life is assessed by FKSI-19
3 years
Quality of Life (QoL) assessed by EQ-5D-5L
Time Frame: 3 years
Quality of life is assessed by EQ-5D-5L.
3 years
Pain Score
Time Frame: 3 years
Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis.
3 years

Collaborators and Investigators

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

Sponsor

Hao Zeng

Investigators

  • Principal Investigator: Hao Zeng, Doctor, 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

Helpful Links

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 (Estimated)

August 1, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

July 14, 2024

First Submitted That Met QC Criteria

July 25, 2024

First Posted (Actual)

July 26, 2024

Study Record Updates

Last Update Posted (Actual)

July 26, 2024

Last Update Submitted That Met QC Criteria

July 25, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VORSIN-RCC

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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