- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04146831
Sintilimab in FH-deficient Renal Cell Carcinoma
Phase II Study of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare subtype of RCC characterized by germline/somatic mutation of the fumarate hydratase (FH) gene, and is an extremely aggressive tumor, with a propensity to disseminate early even in the setting of a small primary tumor.
Loss-of-function mutation of FH results in the accumulation of fumarate, impairment of oxidative phosphorylation, alteration of the metabolic state, and stabilization of hypoxia-inducible factor (HIF)-1α, thus activating angiogenic and oxidative stress response pathways. Unlike the robust response of clear cell RCC (ccRCC) to antiangiogenic agents, blocking the antiangiogenic pathway does not lead to better outcomes in FH-deficient RCC. Anti-mTOR agents are also ineffective.
Although the National Comprehensive Cancer Network (NCCN) guideline recommends the combination of bevacizumab plus erlotinib or everolimus for metastatic FH-deficient RCC, high-level evidence for standardized systematic therapy remains scarce.
In the present study, the investigators plan to assess the efficacy and safety of immunotherapy with Sintilimab as second-line treatment in FH-deficient RCC, and to explore potential biomarkers related to the treatment efficacy by means of detection, including but not limited to the next-generation sequencing, flow cytometry, etc.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥18 years old;
- histopathological evidence of FH-deficient renal cell carcinoma, which was confirmed by Sanger or next-generation sequencing after initial screening by IHC.
- included patients must be diagnosed with metastatic renal cell carcinoma or have a TNM stage IV (according to 2009 TNM Classification). Patients must have received treatment of targeted agents or immunotherapy (including cytokine therapy) before enrollment.
- ECOG score ≤2;
- life expectancy ≥ 3 months;
- sign informed consent, and be able to follow the visit and related procedures stipulated in the program;
- agree to collect tumor tissue, blood and other specimens required by this study and apply them to relevant studies;
- important organs and bone marrow functions meet the following requirements: absolute neutrophil count (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin (HGB) ≥9g/dL;Liver function: serum total bilirubin (TBIL) ≤1.5 times normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 times ULN, serum albumin (ALB) ≥ 2.8g /dL. Renal function: serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥40 mL/min
Exclusion Criteria:
- patients with other malignant tumors with different primary sites or histology from the tumor evaluated in this study within 2 years of personal history, except those with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or cervical carcinoma in situ under good control;
- major surgery or severe trauma within 4 weeks before enrollment;
- immunosuppressive drugs were used within 4 weeks prior to the first dose of study therapy, excluding local glucocorticoids, inhaled or otherwise, or systemic glucocorticoids at physiological doses (i.e., no more than 10mg/ d prednisone or equivalent doses of other glucocorticoids);
- known or suspected active autoimmune diseases (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis, etc. Patients with type 1 diabetes with good insulin control can also be enrolled.
- known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
- allergic to any component of monoclonal antibody;
- suffering from other uncontrolled serious diseases, including but not limited to: A) severe infection in the active phase or clinically poorly controlled; B) HIV infection (HIV antibody positive); C) acute or chronic active hepatitis b (HBsAg positive and HBV DNA>1*103/ml) or acute or chronic active hepatitis c (HCV antibody positive and HCV RNA>15IU/ml); D) active tuberculosis, etc.;
- class iii-iv congestive heart failure (New York heart association classification), poorly controlled and clinically significant arrhythmia;
- uncontrolled arterial hypertension (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg);
- had any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, etc. within 6 months before the selected treatment;
- diseases requiring the use of warfarin (coumarin) for anticoagulant treatment;
- uncontrolled hypercalcemia (more than 1.5 mmol/L of calcium or calcium greater than 12 mg/dL or adjusted serum calcium greater than ULN), or symptomatic hypercalcemia requiring continued bisphosphate treatment;
- accompanied by other malignant tumors (except those that have been cured, such as cervical carcinoma in situ, non-melanoma skin cancer, etc.);
- other acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that may result in increased risk associated with study participation or study drug administration, or interference with the interpretation of study results, and ineligibility to participate in the study as determined by the investigator;
- pregnant or lactating women.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Sintilimab
Sintilimab is administered in this arm.
|
Sintilimab: intravenous, 200mg, every 3 week.
Course of treatment: Stop the treatment until clinical or radiographic progression occurs.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
6-month PFS rate (6 month progression-free survival rate)
Time Frame: Up to 24 months
|
Disease progression was defined as the time from first administration of Sintilimab to progression of disease (PD) or death, according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
|
Up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Up to 24 months
|
Complete response (CR) or partial response (PR) by Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
|
Up to 24 months
|
Duration of response (DOR)
Time Frame: Up to 24 months
|
DOR is defined as the time from the date of first remission to the date of disease progression or death.
|
Up to 24 months
|
Progression-free survival (PFS)
Time Frame: Up to 24 months
|
PFS is defined as the time from first administration of Sintilimab to the date of disease progression or death according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
|
Up to 24 months
|
Overall survival (OS)
Time Frame: Up to 24 months
|
OS is defined as the time from first administration of Sintilimab to the date of death according to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).
|
Up to 24 months
|
Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (FKSI-19)
Time Frame: Up to 24 months
|
FKSI-19 score change over time from baseline to disease progression.
The scale of FKSI-19 is from 0 to 48, and higher scores indicate worse quality of life.
|
Up to 24 months
|
Functional Assessment of Cancer Therapy- Kidney Symptom Index- Disease related Symptoms (FKSI-DRS)
Time Frame: Up to 24 months
|
FKSI-DRS score change over time from baseline to disease progression.
The scale of FKSI-DRS is from 0-36, and higher scores indicate worse quality of life.
|
Up to 24 months
|
EuroQol five-dimension scale (EQ-5D)
Time Frame: Up to 24 months
|
EQ-5D-5L score change over time from baseline to disease progression.
The EQ-5D-5L is consisted of five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).
Higher scores indicate poorer health.
|
Up to 24 months
|
Visual analogue scale (VAS)
Time Frame: Up to 24 months
|
VAS pain score change over time from baseline to disease progression.
The scale of VAS is from 0-10, and higher scores indicate worse symptom of pain.
|
Up to 24 months
|
Frequency of treatment-related adverse events (AEs)
Time Frame: Up to 24 months
|
Records were made according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
|
Up to 24 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory objectives
Time Frame: Up to 24 months
|
To explore the correlations of genes detected by next-generation sequencing, MRI-based response patterns and biomarkers of peripheral blood with the efficacy of Sinitilimab.
|
Up to 24 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CIBI30820191025
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Renal Cell Carcinoma
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Renal Cell Carcinoma | Metastatic Clear Cell Renal Cell Carcinoma | Advanced Clear Cell Renal Cell Carcinoma | Stage III Renal Cell Cancer AJCC v8 | Stage IV Renal Cell Cancer AJCC v8 | Metastatic Sarcomatoid Renal Cell Carcinoma | Advanced Renal Cell Carcinoma | Unresectable Renal Cell... and other conditionsUnited States
-
Australian and New Zealand Urogenital and Prostate...RecruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11.2 Translocation-Related Renal Cell CarcinomaAustralia
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell CarcinomaUnited States
-
National Cancer Institute (NCI)CompletedClear Cell Renal Cell Carcinoma | Recurrent Renal Cell Carcinoma | Stage IV Renal Cell Cancer | Type 1 Papillary Renal Cell Carcinoma | Type 2 Papillary Renal Cell CarcinomaUnited States, Taiwan, Australia
-
Bradley A. McGregor, MDBristol-Myers Squibb; ExelixisRecruitingRenal Cell Carcinoma | Chromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Collecting Duct Renal Cell Carcinoma | Translocation Renal Cell Carcinoma | Unresectable Advanced Renal Cell Carcinoma | Metastatic Ncc Renal Cell CarcinomaUnited States
-
Jonsson Comprehensive Cancer CenterBeiGene; Driven To CureWithdrawnMetastatic Renal Cell Carcinoma | Stage IV Renal Cell Cancer AJCC v8 | Papillary Renal Cell Carcinoma | Collecting Duct Carcinoma | Unresectable Renal Cell Carcinoma | Hereditary Leiomyomatosis and Renal Cell Carcinoma | Clear Cell Papillary Renal Neoplasm | Hereditary Papillary Renal Cell Carcinoma and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingChromophobe Renal Cell Carcinoma | Papillary Renal Cell Carcinoma | Unclassified Renal Cell Carcinoma | Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma | Fumarate Hydratase Deficient Renal Cell Carcinoma | Succinate Dehydrogenase Deficient Renal Cell Carcinoma | Collecting Duct Renal...United States
-
Australian and New Zealand Urogenital and Prostate...Bristol-Myers SquibbActive, not recruitingRenal Cell Carcinoma | Sarcomatoid Renal Cell Carcinoma | Papillary Renal Cell Carcinoma Type 1 | Papillary Renal Cell Carcinoma Type 2 | Chromophobe Renal Cell Carcinoma | Xp11 Translocation CarcinomaAustralia
-
Peloton Therapeutics, Inc.Active, not recruitingKidney Cancer | Renal Cell Carcinoma | Renal Cancer | Renal Cell Carcinoma (RCC) | Renal Cell Cancer Metastatic | Kidney | Clear Cell Renal Cell Carcinoma (ccRCC) | Renal Cell Carcinoma Recurrent | Renal Cell Cancer, RecurrentUnited States
-
AmgenCompletedRenal Cell Carcinoma | Clear Cell Renal Cell Carcinoma | Clear Cell Renal Carcinoma | Renal Cell AdenocarcinomaFrance, United States, Germany
Clinical Trials on Sintilimab
-
Beijing Tiantan HospitalRecruiting
-
RemeGen Co., Ltd.Recruiting
-
Innovent Biologics (Suzhou) Co. Ltd.CompletedAdvanced or Metastatic NSCLCChina
-
Innovent Biologics (Suzhou) Co. Ltd.Innovent Biologics (USA), Inc.WithdrawnMetastatic Cutaneous Melanoma | Unresectable Cutaneous MelanomaUnited States, Germany, France, Australia, Spain, Switzerland, United Kingdom
-
Zhejiang Cancer HospitalRecruitingEsophageal Squamous Cell CarcinomaChina
-
Peking Union Medical College HospitalRecruiting
-
The First Hospital of Jilin UniversityActive, not recruitingLocally Advanced Rectal Cancer | PD-1 | Total Neoadjuvant Treatment | TislelizumabChina
-
Innovent Biologics (Suzhou) Co. Ltd.Completed
-
Wuhan UniversityRecruitingEsophageal Squamous Cell CarcinomaChina
-
Sun Yat-sen UniversityInnovent Biologics (Suzhou) Co. Ltd.UnknownPediatric CancerChina