DV Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple UTUC

Renal Insufficiency Clinical Trial

Official title:

A Prospective, Open-label, Single-arm, Clinical Study of Disitamab Vedotin Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple Upper Urinary Tract Urothelial Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06354231
• Other study ID #: RC48-C012
• Status: Recruiting
• Phase: Phase 2
• Start date: July 20, 2023
• Est. completion date: December 30, 2026

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: Dingwei Ye, Doctor
• Phone: 64175590-82800
• Email: dwyeli[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Approximately 20 participants will be enrolled in the study to evaluate the efficacy and safety of the combination of DV (DV, 2.0 mg/kg, intravenously administered every 2 weeks) and toripalimab (toripalimab, 3.0mg/kg, intravenously administered every 2 weeks). Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy. Efficacy and safety were evaluated by cystoscopy, ureteroscopy, laboratory tests, and imaging examinations after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 30, 2026
• Est. primary completion date: December 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =18 years old;
• Histologically confirmed isolated renal or renal insufficiency or bilateral upper urinary tract urothelial carcinoma;
• Refusal or ineligibility for RNU;
• Preoperative risk stratification was defined as high-risk UTUC, defined as patients

with any of the following factors:

1. Hydronephrosis;

2. Tumor diameter =2cm;

3. Urine cytology suggests a high-grade tumor;

4. A ureteroscopic biopsy suggests a high-grade tumor;

5. CT showed a localized invasion;

6. Multifoci diseases;

7. With multiple histological subtypes;

• ECOG 0~1;
• Major organ function is normal (14 days prior to enrollment) if the following criteria

are met:

1. The blood routine examination criteria should meet (no blood transfusion and no granulocyte colony stimulation agent treatment within 14 days before enrollment): HB=90 g/L; ANC=1.5×109 /L; PLT=100×109 /L;

2. Non-functional organic diseases shall meet the following criteria: T-BIL=1.5×ULN (upper limit of normal value); ALT and AST=2.5 x ULN; Serum creatinine =2×ULN, or endogenous creatinine clearance = 30ml/min(Cockcroft-Gault formula);

• Subjects (or their legal representatives) must sign an informed consent form (ICF) indicating that they understand the purpose and procedures of the study and are willing to participate in the study.
• Pregnant women must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days before the first administration of the randomized or study drug.

Exclusion Criteria:

• Histopathological examination revealed any small cell component of ureter or pelvis, simple adenocarcinoma, simple squamous cell carcinoma, or simple squamous CIS;
• Previous treatment with other PD-1/PD-L1 inhibitors and/or HER-2 inhibitors;
• Active malignancies other than the disease being studied for treatment (i.e., disease progression within the last 24 months or requiring a change in treatment), only the following special cases are allowed: i. Skin cancer that has been treated within the last 24 months and has been completely cured ii. Adequately treated lobular carcinoma in situ (LCIS) and ductus CIS iii. History of local breast cancer and is receiving antihormonal drugs or history of local prostate cancer (N0M0) and is receiving androgen blocking therapy;
• History of uncontrolled cardiovascular disease, including: 1) any of the following in the past 3 months: unstable angina pectoris, myocardial infarction, ventricular fibrillation, torsion ventricular tachycardia, cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; 2) QTc interval prolongation confirmed by ECG evaluation at screening (Fridericia; QTc > 480 ms); 3) Pulmonary embolism or other venous thromboembolism within the past 2 months;
• Pregnant or lactating women;
• Human immunodeficiency virus (HIV) infection is known unless the subject has been on stable antiretroviral therapy for the past 6 months or longer, has not developed an opportunistic infection in the past 6 months, and has a CD4 count > 350 in the past 6 months.
• Known history of clinically significant liver disease, including viral hepatitis [active HBV infection, i.e., HBV DNA positive (>1×104 copies /mL or >2000 IU/ml) must be excluded for known hepatitis B virus (HBV) carriers; Known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103 copies /mL), or other hepatitis, cirrhosis];
• Have not recovered from the toxic effects of previous anticancer treatment (except for those that are not clinically significant, such as hair loss, skin discoloration, neuropathy, and hearing impairment);
• Delayed wound healing, defined as skin/bedsore ulcers, chronic leg ulcers, known stomach ulcers, or non-healing of incisions;
• Major surgery within 4 weeks before day 1 of Cycle 1 (TURBT is not considered a major surgery);
• Other patients assessed by the investigator as unsuitable for participation in the study.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Renal Insufficiency
• Ureteral Neoplasms

Intervention

Drug:
• DV
2.0 mg/kg, intravenously administered every 2 weeks
• Toripalimab
3.0mg/kg, intravenously administered every 2 weeks

Procedure:
• Laser surgery
Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kidney-intact disease-free survival, KI-DFS	Defined as the time to systemic relapse or death.	Up to 12 months
Secondary	Time to progression, TTP	Defined as the time to systemic progression or death.	Up to 3 years
Secondary	Time to RNU	Defined by time from day of first treatment to RNU.	Up to 3 years
Secondary	Disease-specific survival time, DSS	Defined by time from day of first treatment to death due to a specific disease, reflecting the clinical benefit of a specific disease.	Up to 3 years
Secondary	Overall survival	Defined by time from day of first treatment to death.	Up to 3 years
Secondary	3m complete remission	CR is defined by CT urography	Up to 3 years