Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma
Study Details
Study Description
Brief Summary
This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab injection combined with Inlyta in fumarate hydratase-deficient renal cell carcinoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Our previous genetic research as well as other published data indicated the possible well response to combination of immunotherapy with targeted therapy in FH-deficient renal cell carcinoma, therefore the investigators intented to perform this single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab injection combined with Inlyta in FH-deficient renal cell carcinoma.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sintilimab injection combined with Inlyta Sintilimab injection 10ml: 100mg, 200mg intravenously, once every three weeks. Course of treatment: discontinue medication when the disease progresses clinically or radiologically. Inlyta 5mg orally, twice a day. Course of treatment: continue treatment as long as a clinical benefit is observed, or until an unacceptable toxicity is present that cannot be controlled by combination or dose adjustment. In the whole research process, if the disease progresses, the attending doctor has the right to carefully choose other anti-tumor methods, including radiotherapy, chemotherapy and other targeted drugs. |
Drug: Sintilimab injection plus Inlyta treatment
Combined Sintilimab injection and Inlyta treatment in FH-deficient RCC
|
Outcome Measures
Primary Outcome Measures
- PFS [3 years]
progression-free survival
- ORR [3 years]
objective response rate
Secondary Outcome Measures
- OS [3 years]
overall survival
- life quality [Up to 36 months]
evaluate life quality using EuroQol-5D utility score (EQ-5D index) and the EQ-5D visual analogue scale (EQ-VAS) responses. Higher scores indicate poorer health.
Other Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [3 years]
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0, also types and degree
Eligibility Criteria
Criteria
Inclusion Criteria:
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age ≥ 18;
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histology characteristics accord with FH-deficient RCC;
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gene testing confirms germline and/or somatic FH gene mutation ;
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ECOG (Eastern Cooperative Oncology Group)≤2;
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expected survival >3 months;
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blood routine indexes: neutrophils ≥1.5109, platelets ≥100109, hemoglobin ≥90g/L;
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liver function: bilirubin ≤ normal upper limit 1.5 times, AST≤ normal upper limit 2.5 times;Serum creatinine ≤ 1.5 times of normal upper limit;Serum calcium concentration: ≤12.0 mg/dL;
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coagulation function: PT≤ 1.5 times of normal upper limit;
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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.
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all patients signed informed consent.
Exclusion Criteria:
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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;
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renal decompensation requires hemodialysis or peritoneal dialysis;
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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;
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severe active clinical infection;
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patients with coagulation disorder or bleeding constitution;
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major surgery or severe trauma was performed within 4 weeks before enrollment;
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a history of allogeneic organ transplantation or bone marrow transplantation;
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drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results;
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known or suspected allergy to the study drug;
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those who received treatment other than this study within 4 weeks prior to and during the study period.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | West China Hospital | Chengdu | Sichuan | China | 610000 |
Sponsors and Collaborators
- West China Hospital
Investigators
- Principal Investigator: Hao Zeng, West China Hospital
Study Documents (Full-Text)
More Information
Publications
- Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, Merino M, Trepel J, Zbar B, Toro J, Ratcliffe PJ, Linehan WM, Neckers L. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005 Aug;8(2):143-53.
- Kusmartsev S, Eruslanov E, Kübler H, Tseng T, Sakai Y, Su Z, Kaliberov S, Heiser A, Rosser C, Dahm P, Siemann D, Vieweg J. Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. J Immunol. 2008 Jul 1;181(1):346-53.
- Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS, DeBerardinis RJ. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 2011 Nov 20;481(7381):385-8. doi: 10.1038/nature10642.
- Najjar YG, Rayman P, Jia X, Pavicic PG Jr, Rini BI, Tannenbaum C, Ko J, Haywood S, Cohen P, Hamilton T, Diaz-Montero CM, Finke J. Myeloid-Derived Suppressor Cell Subset Accumulation in Renal Cell Carcinoma Parenchyma Is Associated with Intratumoral Expression of IL1β, IL8, CXCL5, and Mip-1α. Clin Cancer Res. 2017 May 1;23(9):2346-2355. doi: 10.1158/1078-0432.CCR-15-1823. Epub 2016 Oct 31.
- Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, Whitten D, Min BW, Tan MH, Zhang Z, Yang XJ, Zhou M, Gardie B, Molinié V, Richard S, Tan PH, Teh BT, Furge KA. An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma. Cancer Cell. 2011 Oct 18;20(4):511-23. doi: 10.1016/j.ccr.2011.08.024.
- Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomäki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA; Multiple Leiomyoma Consortium. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet. 2002 Apr;30(4):406-10. Epub 2002 Feb 25.
- Voss MH, Molina AM, Chen YB, Woo KM, Chaim JL, Coskey DT, Redzematovic A, Wang P, Lee W, Selcuklu SD, Lee CH, Berger MF, Tickoo SK, Reuter VE, Patil S, Hsieh JJ, Motzer RJ, Feldman DR. Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma. J Clin Oncol. 2016 Nov 10;34(32):3846-3853. doi: 10.1200/JCO.2016.67.9084.
- Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Cañamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, McDermott DF. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun. 2016 Aug 30;7:12624. doi: 10.1038/ncomms12624.
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