Clinical trial NCT05220267: Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma
Official title: Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non Clear Cell Renal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-02-02
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The combination of immune checkpoint inhibitors (ICIs) plus angiogenesis inhibitors has demonstrated significant anti-tumor activity in certain cancer. The goal of this study was to evaluate the efficacy and safety of sintilimab (a human programmed death-1 ICI) plus anlotinib (a multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling) in advanced non clear cell renal cell carcinoma.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily joined the study and signed informed consent;
* Aged \> 18 years;
* ECOG body status score is 0 or 1,Expected survival time is greater than 3 months.
* Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
* Patients must have measurable lesions as defined by the RECIST 1.1 standard;
* Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment:

  1. Absolute neutrophil count (ANC) ≥1.5x 109/L
  2. Lymphocyte count ≥ 500/uL.
  3. Platelet count ≥ 80x109/L.
  4. Hemoglobin ≥ 80 g/L (patients may be transfused to meet this criterion).
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver/bone metastases should have AST and ALT ≤ 5 x ULN.
  6. Serum bilirubin ≤ 1.5 x ULN.
  7. Creatinine clearance ≥ 60 mL/min.
  8. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 4 weeks after the last dose of anlotinib or sintilimab.
* Signed informed consent form.
* Ability and capacity to comply with study and follow-up procedures.

Exclusion Criteria:

* Those who are known to be allergic to pharmaceutical ingredients.
* Receive anti-tumor monoclonal antibody or other research drugs within 4 weeks before enrollment; have received other anti-PD-1 antibody therapy or other treatment for PD-1/PD-L1;
* Previous use of anlotinib or other angiogenesis inhibitors
* The patient has any active autoimmune disease or a history of autoimmune disease;
* There are uncontrolled heart clinical symptoms or diseases;
* Patients with congenital or acquired immune deficiency;
* Receive chemotherapy, targeted therapy, radiotherapy within 2 weeks before enrollment;
* A history of gastrointestinal perforation or major surgery within 4 weeks before enrollment;
* Overactive/venous thrombosis occurred within 6 months prior to enrollment, such as cardiovascular-cerebral vascular (including transient ischemic attack),deep vein thrombosis (except for patients who have recovered from venous catheterization due to previous chemotherapy)and pulmonary embolism;
* Those with active bleeding or bleeding tendency;
* Presence of a drug uncontrolled hypertension;
* Urine routine indicates more than urinary protein 2+;
* Correct QT interval \> 470msec; if the patient has a prolonged QT interval, but the investigator's study evaluates that the prolongation is due to a cardiac pacemaker (and no other abnormalities in the heart), it is necessary to discuss with the sponsor's researcher to determine if the patient is Suitable for group study;
* Patients suspected of having other primary cancers;
* Those who are known to be allergic to pharmaceutical ingredients.
* Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening). Patients with past/resolved HBV infection (defined as having negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. A negative HBA DNA test must be obtained in patients with positive hepatitis B core antibody prior to Cycle 1 Day 1.
* Active hepatitis C infection. Patients positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
* Pregnant or lactating women.

Primary outcomes:
measure: progression-free survival (PFS)
timeFrame: up to 2 years
Secondary outcomes:
measure: objective response rate (ORR)
timeFrame: up to 2 years
measure: disease control rate (DCR)
timeFrame: up to 2 years
measure: overall survival (OS)
timeFrame: up to 2 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Center, Sun Yat-sen University
state: Guangdong
Study officials:
References:
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