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

Primary Purpose

Non-clear Renal Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Axitinib
Sponsored by
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-clear Renal Cell Carcinoma focused on measuring toripalimab, axitinib, postoperative adjuvant therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing UniversityRecruiting
  • Hongqian GuoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

study group

Arm Description

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

Outcomes

Primary Outcome Measures

DFS
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
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
Localised disease recurrence-specific survival
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
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

Full Information

First Posted
December 17, 2022
Last Updated
March 13, 2023
Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
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1. Study Identification

Unique Protocol Identification Number
NCT05768464
Brief Title
Postoperative Adjuvant Therapy for Non-clear Renal Cell Carcinoma With High-risk Recurrence Factors
Acronym
IUNU-RC
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 30, 2026 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-clear Renal Cell Carcinoma
Keywords
toripalimab, axitinib, postoperative adjuvant therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
study group
Arm Type
Experimental
Arm Description
Drug: Toripalimab 240mg, intravenously every 3 weeks Drug: Axitinib 5 mg orraly twice daily
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Other Intervention Name(s)
anti-PD-1 monoclonal antibody
Intervention Description
240mg intravenously every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Axitinib
Other Intervention Name(s)
TKI
Intervention Description
5mg orraly twice daily
Primary Outcome Measure Information:
Title
DFS
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
OS
Description
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.
Time Frame
3 years
Title
DRSS
Description
Localised disease recurrence-specific survival
Time Frame
3 years
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
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
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
shun zhang
Phone
15050589789
Email
explorershun@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
hongqian guo
Organizational Affiliation
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shun Zhang
Phone
15050589789
Ext
15050589789
Email
explorershun@126.com
Facility Name
Hongqian Guo
City
Nanning
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongqian Guo, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32775427
Citation
Liu T, Zhang M, Sun D. Immune Cell Infiltration and Identifying Genes of Prognostic Value in the Papillary Renal Cell Carcinoma Microenvironment by Bioinformatics Analysis. Biomed Res Int. 2020 Jul 25;2020:5019746. doi: 10.1155/2020/5019746. eCollection 2020.
Results Reference
background
PubMed Identifier
35596618
Citation
Lobo J, Ohashi R, Amin MB, Berney DM, Comperat EM, Cree IA, Gill AJ, Hartmann A, Menon S, Netto GJ, Raspollini MR, Rubin MA, Tan PH, Tickoo SK, Tsuzuki T, Turajlic S, Zhou M, Srigley JR, Moch H. WHO 2022 landscape of papillary and chromophobe renal cell carcinoma. Histopathology. 2022 Oct;81(4):426-438. doi: 10.1111/his.14700. Epub 2022 Jun 10.
Results Reference
background
PubMed Identifier
22698386
Citation
Steffens S, Janssen M, Roos FC, Becker F, Schumacher S, Seidel C, Wegener G, Thuroff JW, Hofmann R, Stockle M, Siemer S, Schrader M, Hartmann A, Kuczyk MA, Junker K, Schrader AJ. Incidence and long-term prognosis of papillary compared to clear cell renal cell carcinoma--a multicentre study. Eur J Cancer. 2012 Oct;48(15):2347-52. doi: 10.1016/j.ejca.2012.05.002. Epub 2012 Jun 13.
Results Reference
background

Learn more about this trial

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

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