Back to resultsA Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
Primary Purpose
Renal Cell Carcinoma, First-line Treatment, Non Clear Cell Renal Cell Carcinoma
Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
AK104
Axitinib
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma
Eligibility Criteria
Inclusion Criteria: age≥18, ≤75; histology characteristics accord with special pathological subtypes of RCC: papillary renal cell carcinoma, chromophobic cell carcinoma, TFE3 rearrangement renal cell carcinoma, FH-deficient renal cell carcinoma, collecting duct carcinoma, medullary carcinoma, sarcomatoid carcinoma (>10%), unclassified renal cell carcinoma ; metastatic renal cell carcinoma (TNM IV stage according to the 2009 TNM Staging system). Patients who have not previously received systemic therapy, ECOG (Eastern Cooperative Oncology Group)≤2; expected survival >3 months; all patients signed informed consent. blood routine indexes: neutrophils ≥1.5*109, platelets ≥100*109, hemoglobin ≥90g/L; liver function: bilirubin ≤ normal upper limit 1.5 times, ALT/AST≤ normal upper limit 2.5 times;Serum creatinine ≤ 1.5 times of normal upper limit the following diseases did not appear within 12 months: myocardial infarction, severe or unstable angina pectoris, asymptomatic heart failure, cardiovascular and cerebrovascular accident or transient ischemic attack, etc. Exclusion Criteria: other malignancies previously or at the same time that are different from the primary site or histology of the tumor assessed in this study, except cervical carcinoma in situ, basal-cell carcinoma that has been fully treated, superficial bladder tumor (Ta, Tis, T1) or other malignancies that occurred before the enrollment and have been cured for more than 3 years; renal decompensation requires hemodialysis or peritoneal dialysis; arrhythmia need anti-arrhythmic treatment, symptomatic coronary artery disease or myocardial ischemia (myocardial infarction), nearly six months, or congestive heart failure than NYHA Ⅱ level; Hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) that has been treated with 2 or more antihypertensive treatments and still cannot be controlled; severe active clinical infection; patients with coagulation disorder or bleeding constitution; major surgery or severe trauma was performed within 4 weeks before enrollment; a history of allogeneic organ transplantation or bone marrow transplantation; drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results; known or suspected allergy to the study drug; those who received treatment other than this study within 4 weeks prior to and during the study period.
Sites / Locations
- West China Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Combination treatment group
Arm Description
Subjects in this group will receive AK104 (RP2D, administered intravenously) plus Axitinib 5 mg bid, administered orally.
Outcomes
Primary Outcome Measures
ORR per RECIST v1.1 and imRECIST as assessed by investigators
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 and imRECIST
12-month PFS rate per RECIST v1.1 and imRECIST as assessed by investigators
Progression is assessed by investigators based on RECIST v1.1 and imRECIST, including disease progression or death from any cause.
Secondary Outcome Measures
DCR per RECIST v1.1 and imRECIST as assessed by investigators
ORR is the proportion of subjects with complete response(CR), partial response(PR) or stable disease (SD) based on RECIST v1.1 and imRECIST
OS
OS is the time from the first use of a therapeutic drug to death from any cause
PFS per RECIST v1.1 and imRECIST as assessed by investigators
PFS is the time from the first use of a therapeutic drug to disease progression or death from any cause, progression is assessed by investigators based on RECIST v1.1 and imRECIST
Life quality Questionnaire composite
Evaluate life quality using EuroQol Five Dimensions Questionnaire (EQ-5D). EQ-5D included two aspects: EQ-5D Descriptive System and the EQ-5D visual analogue scale (EQ-VAS).
In the description system, health status will be evaluated in 5 aspects: Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression.
EQ-VAS ranges from 0 to 100, higher scores indicate better health.
Pain score
Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05808608
Brief Title
A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
Official Title
A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Hao Zeng
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a Phase Ib/II, open-label, single arm trial to evaluate the efficacy and safety of AK104 in combination with axitinib as a first-line treatment for advanced/metastatic special pathological subtypes of renal cell carcinoma (ssRCC). Subjects will receive AK104 plus axitinib until disease progression, development of unacceptable toxic effects, death, a decision by the physician or patient to withdraw from the trial. The primary endpoint is ORR and PFS per RECIST v1.1 and imRECIST as assessed by investigators.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma, First-line Treatment, Non Clear Cell Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Combination treatment group
Arm Type
Experimental
Arm Description
Subjects in this group will receive AK104 (RP2D, administered intravenously) plus Axitinib 5 mg bid, administered orally.
Intervention Type
Drug
Intervention Name(s)
AK104
Intervention Description
Anti-PD-1/CTLA-4 bi-specific antibody drug; RP2D intravenously (IV)
Intervention Type
Drug
Intervention Name(s)
Axitinib
Intervention Description
An oral, small molecule, TKI selective for VEGFRs; 5mg bid orally
Primary Outcome Measure Information:
Title
ORR per RECIST v1.1 and imRECIST as assessed by investigators
Description
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 and imRECIST
Time Frame
3 years
Title
12-month PFS rate per RECIST v1.1 and imRECIST as assessed by investigators
Description
Progression is assessed by investigators based on RECIST v1.1 and imRECIST, including disease progression or death from any cause.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
DCR per RECIST v1.1 and imRECIST as assessed by investigators
Description
ORR is the proportion of subjects with complete response(CR), partial response(PR) or stable disease (SD) based on RECIST v1.1 and imRECIST
Time Frame
3 years
Title
OS
Description
OS is the time from the first use of a therapeutic drug to death from any cause
Time Frame
3 years
Title
PFS per RECIST v1.1 and imRECIST as assessed by investigators
Description
PFS is the time from the first use of a therapeutic drug to disease progression or death from any cause, progression is assessed by investigators based on RECIST v1.1 and imRECIST
Time Frame
3 years
Title
Life quality Questionnaire composite
Description
Evaluate life quality using EuroQol Five Dimensions Questionnaire (EQ-5D). EQ-5D included two aspects: EQ-5D Descriptive System and the EQ-5D visual analogue scale (EQ-VAS).
In the description system, health status will be evaluated in 5 aspects: Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression.
EQ-VAS ranges from 0 to 100, higher scores indicate better health.
Time Frame
3 years
Title
Pain score
Description
Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Treatment-related adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree
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;
histology characteristics accord with special pathological subtypes of RCC: papillary renal cell carcinoma, chromophobic cell carcinoma, TFE3 rearrangement renal cell carcinoma, FH-deficient renal cell carcinoma, collecting duct carcinoma, medullary carcinoma, sarcomatoid carcinoma (>10%), unclassified renal cell carcinoma ;
metastatic renal cell carcinoma (TNM IV stage according to the 2009 TNM Staging system).
Patients who have not previously received systemic therapy, ECOG (Eastern Cooperative Oncology Group)≤2;
expected survival >3 months;
all patients signed informed consent.
blood routine indexes: neutrophils ≥1.5*109, platelets ≥100*109, hemoglobin ≥90g/L;
liver function: bilirubin ≤ normal upper limit 1.5 times, ALT/AST≤ normal upper limit 2.5 times;Serum creatinine ≤ 1.5 times of normal upper limit
the following diseases did not appear within 12 months: myocardial infarction, severe or unstable angina pectoris, asymptomatic heart failure, cardiovascular and cerebrovascular accident or transient ischemic attack, etc.
Exclusion Criteria:
other malignancies previously or at the same time that are different from the primary site or histology of the tumor assessed in this study, except cervical carcinoma in situ, basal-cell carcinoma that has been fully treated, superficial bladder tumor (Ta, Tis, T1) or other malignancies that occurred before the enrollment and have been cured for more than 3 years;
renal decompensation requires hemodialysis or peritoneal dialysis;
arrhythmia need anti-arrhythmic treatment, symptomatic coronary artery disease or myocardial ischemia (myocardial infarction), nearly six months, or congestive heart failure than NYHA Ⅱ level; Hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) that has been treated with 2 or more antihypertensive treatments and still cannot be controlled;
severe active clinical infection;
patients with coagulation disorder or bleeding constitution;
major surgery or severe trauma was performed within 4 weeks before enrollment;
a history of allogeneic organ transplantation or bone marrow transplantation;
drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results;
known or suspected allergy to the study drug;
those who received treatment other than this study within 4 weeks prior to and during the study period.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Zeng, Professor
Phone
8618980602129
Email
kucaizeng@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hao Zeng, Professor
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hao Zeng, professor
Phone
8618980602129
Email
kucaizeng@163.com
First Name & Middle Initial & Last Name & Degree
Hao Zeng, professor
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
There is a plan to make IPD and related data dictionaries available
IPD Sharing Time Frame
Data would be available starting from the time when summary data are published or otherwise made available, for 3 years.
IPD Sharing Access Criteria
Other researchers access the data by sending an email to our PI.
Citations:
PubMed Identifier
35346519
Citation
Ljungberg B, Albiges L, Abu-Ghanem Y, Bedke J, Capitanio U, Dabestani S, Fernandez-Pello S, Giles RH, Hofmann F, Hora M, Klatte T, Kuusk T, Lam TB, Marconi L, Powles T, Tahbaz R, Volpe A, Bex A. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. 2022 Oct;82(4):399-410. doi: 10.1016/j.eururo.2022.03.006. Epub 2022 Mar 26.
Results Reference
background
PubMed Identifier
32733094
Citation
Diaz-Montero CM, Rini BI, Finke JH. The immunology of renal cell carcinoma. Nat Rev Nephrol. 2020 Dec;16(12):721-735. doi: 10.1038/s41581-020-0316-3. Epub 2020 Jul 30.
Results Reference
background
PubMed Identifier
29562145
Citation
Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.
Results Reference
background
Citation
2022 ASCO # Oral abstract 106.
Results Reference
background
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A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
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