IUNU-RC: Postoperative Adjuvant Therapy for Non-clear Renal Cell Carcinoma With High-risk Recurrence Factors

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)

Overall Status

Recruiting

CT.gov ID

NCT05768464

Collaborator

(none)

Enrollment

Locations

Arm

58.9

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this prospective, multicenter, single-arm clinical study is to evaluate the efficacy and safety of toripalimab in combination with axitinib for postoperative adjuvant therapy for non-clear renal cell carcinoma with high-risk recurrence factors.

Condition or Disease	Intervention/Treatment	Phase
Non-clear Renal Cell Carcinoma	Drug: Toripalimab Drug: Axitinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Multicenter, Single-arm Clinical Study of the Efficacy and Safety of Toripalimab in Combination With Axitinib for Postoperative Adjuvant Therapy for Non-clear Renal Cell Carcinoma With High-risk Recurrence Factors

Actual Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 30, 2026

Anticipated Study Completion Date :

Dec 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: study group Drug: Toripalimab 240mg, intravenously every 3 weeks Drug: Axitinib 5 mg orraly twice daily	Drug: Toripalimab 240mg intravenously every 3 weeks Other Names: anti-PD-1 monoclonal antibody Drug: Axitinib 5mg orraly twice daily Other Names: TKI

Arm

Intervention/Treatment

Experimental: study group

Drug: Toripalimab 240mg, intravenously every 3 weeks Drug: Axitinib 5 mg orraly twice daily

Drug: Toripalimab

240mg intravenously every 3 weeks

Other Names:

anti-PD-1 monoclonal antibody

Drug: Axitinib

5mg orraly twice daily

Other Names:

TKI

Outcome Measures

Primary Outcome Measures

DFS [2 years]
DFS is defined as time interval from the date of randomization to first date of recurrence/relapse (distant or local recurrence of [RCC] or occurrence of a secondary malignancy {occurrence of a second primary cancer other than RCC} or death). For participants with no DFS event, DFS was censored at date of last scan prior to time of analyses. Participants alive who did not have post-baseline disease assessments, DFS was censored at randomization. Participants who received further anti-tumor therapy prior to recurrence or occurrence of a secondary malignancy or death, DFS was censored on date of last scan prior to taking anti-tumor medication. Participants who missed 2 or more consecutive tumor scans immediately followed by an event were censored at date of last objective tumor assessment prior to missing/not readable scan.

Secondary Outcome Measures

OS [3 years]
OS defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Participants lacking data beyond randomization had their survival times censored at randomization.
DRSS [3 years]
Localised disease recurrence-specific survival
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [3 years]
Incidence and grade of AEs and SAEs per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, incidence of ≥ grade 3 AE

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-75 years old
Participants with histologically confirmed non-clear renal cell carcinoma except clear cell RCC, chromophobe RCC and eosinophilic RCC, and must meet any of the following conditions:
histologically confirmed Papillary RCC, pT≥T1b and ISUP/WHO ≥3, N (any), M0;
Collecting duct carcinoma, SMARCB1-deficient renal medullary carcinoma, fumarate hydratase deficiency renal cell carcinoma (FH-RCC), pT (any), ISUP/WHO (any), N (any), M0.
Non-clear renal cell carcinoma except Organizational Credits Type a and b, including but not limited to TFE3/TFEB translocated RCC or unclassified RCC, pT (any), ISUP/WHO ≥ grade 3, N (any), M0;
Patients who have completely resected the primary tumor (partial or radical nephrectomy), and M1 NED patients who have completely resected solid, isolated soft tissue metastases.
Patients who have completely removed the renal tumor. The nephrectomy must be performed ≥ 3 weeks but ≤ 12 weeks before randomization. Partial nephrectomy and renal tumor enucleation are permitted;
Patients must have no clinical or radiographic evidence of macroscopic residual lesions or distant metastasis (M0) after surgery. M1 participants must have no evidence of disease (M1 NED);
ECOG performance status 0-1 ;
Patients must have not received systemic therapy for renal tumors;
Adequate hematopoiesis and organ function:

Hematopoietic function: Absolute neutrophil count (ANC) ≥1.5×109/L; platelets≥ 100×109/L; Hemoglobin≥ 9.0g/dL;
Renal function: serum creatinine ≤ 1.5 times ULN, or creatinine clearance > 50 mL/min;
Liver function: total bilirubin ≤1.5×ULN or total bilirubin >1.5×ULN but direct bilirubin normal; AST and ALT≤2.5×ULN;
Coagulation function: international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN;
Left ventricular ejection fraction (LVEF) ≥ 50%;

Signed informed consent form;
Patients and/or their partner are willing to use highly effective forms of contraception and to continue its use 3 months after the last dose of drugs.
Ability and capacity to comply with study and follow-up procedures.

Exclusion Criteria:

Clear cell RCC, chromophobe RCC and eosinophilic RCC;
Previous anti-tumor immunotherapy, including but not limited to cytokines (IL-2, IFN-α, etc.) and antibody drugs (anti-PD-1, PD-L1, or CTLA-4 antibodies, etc.)
Previous drug therapy targeting VEGF, VEGFR, or mTOR;
Have participated in or are currently participating in an investigational drug trial within 4 weeks; major surgery performed within 4 weeks prior to randomization;
Receive traditional Chinese medicines or proprietary Chinese medicine, adrenocortical hormone or other immunosuppressant systemic therapy within 2 weeks before enrollment; People who > 10 mg of prednisone or equivalent inhalers daily but have no active autoimmune disease may participate in this study;
Toxicity has not been relieved after previous antineoplastic therapy; Irreversible toxicities (e.g., hearing loss) that are reasonably expected not to be aggravated by the study drug may participate in this study;
Other malignancies that have progressed or require treatment in 5 years (excluding adequately treated basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, superficial bladder cancer, breast, cervix, or prostate carcinoma in situ);
History of central nervous system (CNS) metastases or CNS metastases on baseline imaging (MRI or CT) within 30 days prior to the first trial administration;
Hypertension that cannot be controlled by medications (blood pressure 150/100 mmHg despite optimal medical therapy)
Evidence of following cardiovascular disease within 6 months:
Myocardial infarction
Unstable angina
Cardiac angioplasty or stenting
Coronary/peripheral artery bypass grafting
Class III or IV congestive heart failure as prescribed by the New York Heart Association
Cerebrovascular accident or transient ischemic attack
QT interval (QTc) corrected with heart rate ≥500 msec (Bazett's formula)
History of active or other severe bleeding within 30 days, and have haemoptysis within 6 weeks prior to randomization;
Deep vein thrombosis or pulmonary embolism within 6 months;
Clinically significant gastrointestinal (GI) abnormalities, including:
malabsorption, total gastrectomy or any condition that may affect the absorption of oral medications;
active ulcers treated within the past 6 months;
active gastrointestinal bleeding (e.g., hematemesis, hematochezia, or melena) within the past 3 months with no evidence of healing endoscopic or colonoscopy;
Metastatic lesions of the gastrointestinal tract suspected of bleeding, inflammatory bowel disease, ulcerative colitis, perforation of the digestive tract or other gastrointestinal diseases that increase the risk of perforation;
History of organ transplantation may require long-term adrenocortical hormone therapy;
Previous or current presence of (noninfectious) pneumonia/interstitial lung disease requiring adrenocortical hormone therapy
Active infection requiring systemic treatment, human immunodeficiency virus (HIV) infection (known HIV antibody positive), active HBV or HCV infection;
Have received a live vaccine within 30 days prior to enrollment;
History of severe drug allergy;
Known history of psychiatric illness or substance abuse;
The presence of unhealed wounds;
Taken within 7 days prior to enrollment or expected to take concomitant treatment with potent CYP3A4/5 inhibitors and CYP3A4/5 inducers ;
Subject has a history or current evidence of any disease, treatment, or laboratory abnormality that may confound the trial results, interfere with the subject's participation in the full trial, or is not in the best interest of the subject to participate in the trial, in the judgment of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University	Nanjing	Jiangsu	China	210000
2	Hongqian Guo	Nanning	Jiangsu	China