Trial Title:
Vorolanib Plus Sintilimab for Advanced Renal Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitors Based Combination Therapy
NCT ID:
NCT06523049
Condition:
Renal Cell Carcinoma
Immunotherapy
Molecular Targeted Therapy
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Vorolanib
Conditions: Keywords:
Vorolanib
Sintilimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vorolanib Tablets
Description:
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.
Arm group label:
Combination treatment group
Other name:
Vorolanib
Intervention type:
Drug
Intervention name:
Sintilimab Injection
Description:
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.
Arm group label:
Combination treatment group
Other name:
Sintilimab
Summary:
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).
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital
Address:
City:
Chengdu
Zip:
610000
Country:
China
Contact:
Last name:
Xingming Zhang, Doctor
Phone:
+86-18782258490
Email:
Jarmin@scu.edu.cn
Start date:
August 2024
Completion date:
September 2026
Lead sponsor:
Agency:
Hao Zeng
Agency class:
Other
Source:
West China Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06523049
http://clinicaltrials.gov/study/NCT02501096?term=NCT02501096&rank=1
