Clinical trial NCT06354231: DV Combined With Toripalimab for Renal Preservation in Solitary Kidney or Renal Insufficiency or Bilateral Multiple UTUC
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Renal Insufficiency
Upper Urinary Tract Urothelial Carcinoma
Solitary Kidney
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 20
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Kidney-intact disease-free survival, KI-DFS
timeFrame: Up to 12 months
Secondary outcomes:
measure: Time to progression, TTP
timeFrame: Up to 3 years
measure: Time to RNU
timeFrame: Up to 3 years
measure: Disease-specific survival time, DSS
timeFrame: Up to 3 years
measure: Overall survival
timeFrame: Up to 3 years
measure: 3m complete remission
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Dingwei Ye, Doctor
role: PRINCIPAL_INVESTIGATOR
References: