Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma

Phase 2

Not yet recruiting

• Conditions: Non Clear Cell Renal Carcinoma
• Interventions: Drug: Anlotinib plus Sintilimab

• Registration Number: NCT05220267
• Lead Sponsor: Sun Yat-sen University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-12-24
• Status Verified: 2022-01
• Study First Submitted QC: 2022-02-01
• Last Update Submitted: 2022-02-01
• Study First Posted: 2022-02-02
• Last Update Posted: 2022-02-02
• Study Start: 2022-02-28
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 43

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anlotinib plus Sintilimab	Anlotinib plus Sintilimab	Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle) .Sintilimab was administered intravenously (200mg once every 3weeks).

Primary Outcome Measures

Name	Time	Method
progression-free survival (PFS)	up to 2 years	Time from treatment until disease progression or death

Secondary Outcome Measures

Name	Time	Method
objective response rate (ORR)	up to 2 years	objective response rate (ORR) by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR)
disease control rate (DCR)	up to 2 years	disease control rate (DCR)by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR) and Stable Disease(SD).
overall survival (OS)	up to 2 years	Time from treatment until death from any cause
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	up to 2 years

Trial Locations

Locations (1)

Cancer Center, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China