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Trial Title:
Vorolanib Combined With Cadonilimab in the Treatment of Untreated Advanced RCC Patients
NCT ID:
NCT06577961
Condition:
Kidney Cancer
RCC
Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Vorolanib
Conditions: Keywords:
Kidney Cancer
RCC
Renal Cell Carcinoma
vorolanib Combined with Cadonilimab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Vorolanib combined with cadonilimab
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vorolanib
Description:
stage Ⅰ：Vorolanib 200mg QD stage Ⅱ：Vorolanib RP2D QD
Arm group label:
Experimental group
Other name:
CM082
Intervention type:
Drug
Intervention name:
cadonilimab
Description:
stageⅠ：cadonilimab 10mg/kg Q3W stageⅡ：cadonilimab 10mg/kg Q3W
Arm group label:
Experimental group
Other name:
AK104
Summary:
Evaluate the efficacy and safety of vorolanib combined with cadonilimab in the treatment
of untreated advanced RCC patients.
Detailed description:
This study is a multicenter, prospective, phase I/II single-arm trial, aiming to enroll
37 untreated patients with advanced or metastatic ccRCC to receive vorolanib combined
with cadonilimab treatment, and to perform CTC/ctDNA testing on subjects.
In the phase I dose exploration phase, a 3+3 dose escalation method is used to explore
the safety of vorolanib at the standard dose combined with cadonilimab within one
treatment cycle, and to determine the dose.
In the phase II trial phase, the dosage of vorolanib is determined by the optimal
tolerated dose found in the phase I trial, while cadonilimab is combined for treatment.
Patients need to be evaluated for efficacy and safety after every 2 treatment cycles
(within ±3 days at the end of each cycle), and continue treatment until disease
progression, intolerable toxicity, or completion of the prescribed treatment cycle.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subjects voluntarily participate in this study, willing and able to comply with and
sign the informed consent form;
2. Histologically confirmed clear cell renal cell carcinoma;
3. Advanced (not suitable for curative surgery or radiation therapy) or metastatic
(AJCC Stage IV) RCC;
4. No prior systemic treatment for RCC, except for the following situations:
a) For completely resectable renal cell carcinoma, having received one type of
adjuvant or neoadjuvant treatment, if the treatment does not include drugs targeting
VEGF or VEGFR, and recurrence occurs at least 6 months after the last adjuvant or
neoadjuvant treatment;
5. Confirmed to have at least one measurable lesion according to RECIST 1.1 criteria;
6. KPS score ≥ 70;
7. Expected survival time of more than 3 months;
8. Aged 18-75 years;
9. Good function of major organs and sufficient hematology, meeting the following
criteria:
Absolute neutrophil count (ANC) ≥ 1500 cells/μL (no granulocyte colony-stimulating
factor support within 2 weeks before Cycle 1, Day 1) Platelet count (PLT) ≥ 80 ×
10^9/L. WBC count ≥ 2500/μL without G-CSF, ≤ 15000/μL Lymphocyte count ≥ 500/μL
Hemoglobin ≥ 9.0 g/dL (Cycle 1), not dependent on erythropoietin, and no transfusion
of concentrated red blood cells (pRBC) in the past 2 weeks Alanine aminotransferase
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤ 3 times the
upper limit of normal (ULN) (liver metastasis ≤ 5 times ULN). If the patient has
bone metastasis, ALP ≤ 5 times ULN.
Serum bilirubin ≤ 1.5 × ULN. Patients with known Gilbert's syndrome can be enrolled
if serum bilirubin level ≤ 3 times ULN.
Serum albumin ≥ 2.8 g/dL Creatinine ≤ 2.0 × ULN or calculated creatinine clearance
rate ≥ 30 mL/min. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)
10. For women who are not menopausal (amenorrhea for 12 months) or surgically sterile
(without ovaries and/or uterus): agree to use two appropriate methods of
contraception, including at least one method with an annual failure rate of ≥ 1%.
11. Sexually active subjects of childbearing potential and their partners must agree to
use medically recognized contraceptive methods during the study and for 5 months
after the last dose of study treatment for women and 7 months for men (e.g., barrier
methods, including male condoms, female condoms, or diaphragms coated with
spermicidal gel).
12. Female subjects of childbearing potential must not be pregnant at screening. Women
of childbearing potential are defined as premenopausal women who can become pregnant
(i.e., women who have had any menstrual signs in the past 12 months, except for
those who are surgically sterile as mentioned above).However, women who have been
amenorrheic for 12 months or longer are still considered to have childbearing
potential if the amenorrhea is likely due to previous chemotherapy, anti-estrogens,
low body weight, ovarian suppression, or other reasons.
Exclusion Criteria:
1. Received any systemic treatment for RCC, unless the investigator can provide
evidence that the subject has been randomly assigned to the placebo group;
2. Central nervous system metastasis;
3. Active malignant tumor in the past 24 months (except for renal cell carcinoma, skin
basal cell carcinoma or squamous cell carcinoma that has been clearly treated, as
well as cervical or bladder carcinoma in situ). Participants with a history of
localized and low-risk prostate cancer who have received curative treatment and have
not had a prostate-specific antigen (PSA) recurrence in the past 5 years may
participate in the study;
4. Received prior radiotherapy within 21 days before the start of study treatment
(palliative radiotherapy for bone lesions is allowed, provided it is completed at
least 2 weeks before the start of study treatment);
5. Currently participating in another study or received study drugs within 4 weeks
before the start of study treatment.
6. Receiving live vaccines within 30 days after the planned start of study treatment
(first cycle/day 1). Live vaccines include but are not limited to measles, mumps,
rubella, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid
vaccines. Injectable seasonal influenza vaccines are generally inactivated virus
vaccines and are allowed; however, intranasal influenza vaccines are attenuated live
vaccines and are not allowed.
7. Participants with proteinuria > 1+ on urine dipstick test will undergo a 24-hour
urine collection for quantitative assessment of proteinuria. Participants with
urinary protein ≥ 1g/24h will not be eligible.
8. Fasting total cholesterol > 300 mg/dL (or 7.75 mmol/L) and/or fasting triglyceride
level 2.5 times the upper limit of normal (ULN). Note: These participants can be
included after lipid-lowering treatment.
9. Uncontrolled diabetes defined as fasting blood glucose > 1.5 times the upper limit
of normal. Note: These participants can be included after hypoglycemic treatment.
10. Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or
corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued
bisphosphonate treatment or denosumab.
11. QTc interval prolongation to > 480 ms.
12. Participants who have not fully recovered from any toxicity and/or complications
caused by major surgery before starting treatment.
13. Malabsorption, gastrointestinal anastomosis, or any other condition that may affect
the absorption of study drugs.
14. Clinically significant hematuria, vomiting blood, or coughing up blood > 0.5
teaspoon (2.5 ml) within 12 weeks before the first dose, or other significant
bleeding history (such as pulmonary hemorrhage).
15. Significant cardiovascular impairment within 12 months after the first dose of study
drug: history of congestive heart failure New York Heart Association class II or
higher, unstable angina, myocardial infarction, cerebrovascular accident, or
arrhythmia related to hemodynamic instability. The following conditions are also
excluded: left ventricular ejection fraction (LVEF) below the institutional normal
range determined by gated blood pool scan or echocardiogram.
16. Active infection (any infection requiring systemic treatment).
17. Positive for human immunodeficiency virus (HIV).
18. Active hepatitis B or C.
19. Known history of interstitial lung disease or any evidence.
20. History of (non-infectious) pneumonia requiring steroids, or currently suffering
from pneumonia.
21. Diagnosed with immunodeficiency or receiving chronic systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days before the first study
treatment. Physiological doses of corticosteroids (up to 10 mg/day prednisone or
equivalent) can be used during the study period.
22. Active autoimmune disease requiring systemic treatment within the past 2 years
(excluding psoriasis). Alternative therapies (such as thyroid hormones, insulin, or
physiological corticosteroid replacement therapy for adrenal or pituitary
insufficiency) are not considered forms of systemic treatment.
23. Breastfeeding or pregnant women at screening or baseline.
24. Fertile women who do not agree to use highly effective contraceptive methods
throughout the study period and for 120 days after the end of the study.
25. Men who have not successfully undergone vasectomy (diagnosed with azoospermia) and
do not agree to use condoms/spermicides from the first dose of study treatment until
120 days after the last dose of study treatment, unless they practice abstinence.
26. Known intolerance to any study drug (or any excipient).
27. Participants who have received allogeneic tissue/solid organ transplantation.
28. Patients requiring pain medication must be on a stable treatment regimen at the
start of the study.
29. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage (monthly or more frequently).
30. Uncontrolled hypertension defined as persistent blood pressure (BP) > 150 mmHg
systolic or > 100 mmHg diastolic.
31. Unable to swallow tablets or capsules.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
August 31, 2024
Completion date:
August 31, 2027
Lead sponsor:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06577961
