Trial Title:
Fruquintinib and Serplulimab Combination Therapy for First-line Treatment of Non-clear Cell Renal Cell Carcinoma: A Prospective Multicenter Study
NCT ID:
NCT05831891
Condition:
First-line Treatment of Non-clear Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Conditions: Keywords:
Fruquintinib
Serplulimab
combination therapy
first-line
non-clear renal cell carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single Group Assignment Before surgery, patients will receive Fruquintinib 5mg, qd, 2w
on/1w off, combined with Serplulimab 4.5mg/kg, IV drip, d1, q3w.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib combined with Serplulimab
Description:
Fruquintinib 5mg, qd, 2w on/1w off and Serplulimab 4.5mg/kg, IV drip, d1, q3w
Arm group label:
Fruquintinib combine with Serplulimab
Other name:
Elunate
Other name:
HLX10
Summary:
This study is design to prospectively investigate the safety and efficacy of Fruquintinib
combined with Serplulimab in first-line treatment of non-clear renal cell carcinoma.
Fruquintinib, a vascular endothelial growth factor receptor inhibitor, is an anticancer
drug independently developed in China to treat refractory metastatic colorectal cancer
(mCRC). This is a Single-arm, multicenter, prospective phase 2 clinical study.
Detailed description:
The study is ongoing. This is a single-arm, multicenter clinical study enrolling 39
patients with metastatic or unresectable nccRCC at Renji Hospital and Zhongshan Hospital
in Shanghai, China. The study is divided into a safety-run-in stage and a cohort
expansion stage. Six patients were enrolled in the safety-run-in stage, and no
dose-limited toxicity or treatment-related deaths occurred within the 28-day observation
period. Consequently, the cohort was expanded to 39 patients. The treatment includes
Fruquintinib 5mg, qd, 2w on/1w off, combined with Serplulimab 4.5mg/kg, IV drip, d1, q3w.
Tumor response is evaluated at baseline, every 6 weeks during treatment, and at
end-of-treatment visit.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) Patients who have signed an informed consent form and are willing to complete
the study according to the protocol; 2) Age between 18 and 75 years old; 3)
Patients with metastatic or unresectable nccRCC who have been histologically or
cytologically diagnosed (AJCC 8th edition staging); 4) At least one measurable
lesion, as required by the "Measurable Lesion" criteria in RECIST 1.1; 5) Not
treated with any systemic anti-tumor therapy since diagnosis, including
chemotherapy, targeted therapy, and immunotherapy (including but not limited to
anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, etc.); 6) Expected survival
of 3 months; 7) ECOG score 0-1; 8) Good organ function: meeting the following
requirements:
1. Absolute neutrophil count (ANC) ≥1.5× 109/L;
2. Platelet count ≥100×109/L;
3. Hemoglobin ≥9g/dL;
4. Serum albumin ≥2.8g/dL;
5. Total bilirubin ≤1.5 ×ULN, ALT, AST, and/or ALP ≤3 ×ULN; if liver or bone metastasis
is present, ALP ≤5 ×ULN;
6. Serum creatinine ≤1.5×ULN and creatinine clearance rate 60 mL/min (Cockcroft-Gault,
see Appendix 3);
7. Activated partial thromboplastin time (APTT) and international normalized ratio
(INR) ≤1.5× ULN (patients receiving stable doses of anticoagulant therapy such as
low-molecular-weight heparin or warfarin and whose INR is within the expected
therapeutic range of anticoagulants can be screened); 9) Patients infected with
hepatitis B Virus (HBV) and inactive/asymptomatic carriers, or patients with chronic
or active HBV will be allowed to enroll if their HBV DNA<500 IU/mL (or 2500
copies/mL); HCV antibody-positive patients will be allowed to enroll if HCV-RNA is
negative during screening.
Note: HBsAg-positive patients or patients with detectable HBV DNA who receive
antiviral treatment should undergo treatment for >2 weeks before enrollment, and
continue treatment for 6 months after the study drug treatment.
10) *For women of reproductive age, urine or serum pregnancy test results should be
negative within 7 days or less before treatment. And use a medically approved
contraceptive (such as an intrauterine device, contraceptive or condom) during
the study treatment period and at least 3 months after the last use of
Serplulimab and at least 6 months after the last use of chemotherapy; 11) Male
subjects who are not sterilized must be willing to use a medically approved
contraceptive method (such as an IUD, contraceptive or condom) for the duration
of the study treatment, at least 3 months after the last use of Serplulimab and
at least 6 months after the last use of chemotherapy.
Exclusion Criteria:
-
1) There is a history of allergy to any component of the drug SLT or the drug
Fruquintinib.
2) A history of or concurrent malignancy (excluding skin basal cell carcinoma
and cervical carcinoma in situ and papillary carcinoma of thyroid) that
has been cured for more than 5 years and has no active cancer）.
3) Uncontrolled clinical symptoms or diseases of the heart, including: a)
NYHA class II or above heart failure; b) unstable angina; c) myocardial
infarction within 1 year; d) significant atrial or ventricular arrhythmias
requiring clinical intervention.
4) Having received any of the following treatments: a) previous treatment
with PD-1, PD-L1 antibodies, or CTLA-4 antibodies; b) received any
investigational drugs within 4 weeks prior to the first dose of the study
drug; c) enrolled in another clinical trial, unless it is an observational
(non-interventional) study; d) requiring systemic treatment with
corticosteroids (>10 mg/day prednisone or equivalent) or other
immunosuppressive drugs within 2 weeks prior to the first dose of the
study drug, with the exception of using corticosteroids for local
inflammation or prevention of allergies, nausea, and vomiting. Other
special circumstances should be communicated with the investigator. In the
absence of active autoimmune diseases, inhaled or locally applied steroids
and adrenal cortex hormones that replace a dosage of >10 mg/day prednisone
can be used.
e) Vaccination with anti-tumor vaccines or receipt of live vaccines within 4
weeks prior to the first dose of the study drug; f) underwent major surgery or
had any serious trauma within 4 weeks prior to the first dose of the study
drug.
5) Toxicity from previous anti-cancer therapy has not recovered to ≤ CTCAE
grade 1 (excluding alopecia and residual neurotoxicity related to previous
platinum therapy) or does not meet inclusion/exclusion criteria.
6) Serious infection (CTCAE grade >2) within 4 weeks prior to the first dose
of the study drug, including severe pneumonia, sepsis requiring
hospitalization, and infection-related complications; baseline chest
imaging shows active pulmonary inflammation, symptoms and signs of
infection within 4 weeks of first dose, or the need for oral or
intravenous antibiotics.
7) Active autoimmune diseases or a history of autoimmune diseases (including
but not limited to interstitial pneumonia, colitis, hepatitis,
hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism),
except autoimmune-mediated hypothyroidism treated with a stable dose of
thyroid replacement hormone and I-type diabetes treated with a stable dose
of insulin. Patients with vitiligo or childhood asthma/allergy in
remission without any intervention in adulthood are not excluded.
8) A history of immunodeficiency diseases, including HIV-positive, other
acquired or congenital immunodeficiency diseases, organ transplantation,
or allogeneic bone marrow transplantation.
9) A history of interstitial lung disease (excluding radiation pneumonitis
that has not been treated with steroids), and a history of non-infectious
pneumonia.
10) Evidence of active tuberculosis infection based on medical history and CT
examination, a history of active tuberculosis infection within 1 year
prior to screening, or a history of active tuberculosis infection over 1
year ago that has not been properly treated.
11) Patients with active hepatitis B (HBV DNA ≥500 IU/mL or 2500 copies/mL) or
hepatitis C (positive HCV antibodies and HCV-RNA higher than the detection
limit of the assay) are excluded. Patients with HBsAg-positive and HBV
DNA-negative or HBV DNA <500 IU/mL or 2500 copies/mL can receive treatment
for antiviral therapy for more than 2 weeks before enrolling in the trial
and continue antiviral therapy for 6 months after the end of the last dose
of the study drug.
12) A known history of psychotropic substance abuse, alcoholism or drug use;
13) Pregnant or lactating women; 14) At the investigator's discretion,
patients with other factors that may force them to withdraw from the
study, such as concomitant severe illnesses (including mental illness)
requiring treatment, significant laboratory abnormalities, and family or
social factors that may hinder patient safety or data collection.
15) Patients with severe active bleeding, active peptic ulcers, unhealed
gastrointestinal perforations, or gastrointestinal fistulas.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
June 30, 2023
Completion date:
July 31, 2026
Lead sponsor:
Agency:
RenJi Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
RenJi Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05831891
