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Carcinoma, Renal CellPhase 2NCT04387500

Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma

A Phase 2 study testing Sintilimab injection plus Inlyta treatment in people with Carcinoma, Renal Cell and Fumarate Hydratase Deficiency, run by West China Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sintilimab injection plus Inlyta treatment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteChina
Study dates
1 Jul 2021to 1 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18, no gender limitation;
  • Histopathological confirmed RCC, and diagnosed as FH-dRCC by Sanger or NGS sequencing after being included in preliminary IHC screening;
  • The patients incuded must be diagnosed with metastatic RCC or TNM stage IV (according to the 2009 TNM staging system), with distant metastasis confirmed by radiology or pathology.
  • Have not received systemic treatment, including cytokines, targeted drugs, or other experimental drugs, or have received targeted drugs (within the range of 1st-line targeted drugs recommended by NCCN2022 for renal cancer) with single drug treatment for less than 1 month and have completed the washout period. ECOG score ≤ 2;
  • Life expectancy ≥ 3 months;
  • Signed written informed consent form and willing and able to comply with scheduled visits and other requirements of the study；
  • Agree to collect tumor tissue and blood samples required for this study and apply the samples to relevant studies;
  • Adequate organ and bone marrow function: absolute neutrophil count (ANC): ≥1×109/L, platelet count (PLT) ≥50×109/L, hemoglobin content (HGB) ≥80g/L; Liver function: total bilirubin (TBIL) ≤3×normal upper limit (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5×ULN, albumin ≥20g/L; Renal function: serum creatinine (Cr) ≤3×ULN.

Who cannot join

  • Previously received anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 antibody, or any other antibodies or drugs specifically targeting co-stimulatory or checkpoint pathways of T cells;
  • Active brain metastasis;
  • Other malignancy with primary site or histological type different from tumors evaluated in this study within 2 years of personal history, except skin basal cell carcinoma, squamous cell carcinoma or adequately treated cervical carcinoma in situ;
  • Underwent major operation (craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study medication or with severe trauma;
  • Received systemic treatment with corticosteroids (> 10mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
  • Known or suspected active autoimmune disease (congenital or acquired), including interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. Patients with type I diabetes, hypothyroidism that only requires systemic treatment (including vitiligo, psoriasis, alopecia, etc.), or conditions that are not expected to recur in the absence of external triggers are eligible to participate in this study; Known history of allogeneic organ (except corneal transplantation) or allogeneic hemopoietic stem cell transplantation;
Show all 19Show fewer
  • Known allergy or hypersensitivity to any monoclonal antibodies or any components used in their preparation;
  • Uncontrolled concomitant disease, including but not limited to:
  • Active or poorly controlled severe infection;
  • Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
  • Known acute or chronic active hepatitis B infection (HBsAg positive and HBV DNA>1*103/ml), or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA>15IU/ml);
  • Active tuberculosis;
  • Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia;
  • Poorly controlled arterial hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) with standard treatment;
  • Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack, within 6 months of enrollment;
  • Diseases that require anticoagulant treatment with warfarin (coumarin);
  • Poorly controlled hypercalcemia (Ca2+ > 1.5mmol/L, or serum calcium > 12mg/dL, or corrected serum calcium > ULN), or symptomatic hypercalcemia requiring bisphosphate treatment;
  • Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study;
  • Women who are pregnant or nursing.

Trial locations and contacts

1 site in 1 country.

China1 site

  • West China Hospital

    Chengdu, Sichuan, 610000

Other trials in China

About this study

Official title: 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

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.

Read the 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.

Being tested
Sintilimab injection plus Inlyta treatment
Keywords
Sintilimab, Inlyta
Medical subject headings
Carcinoma, Renal Cell, Fumaric aciduria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sintilimab injection plus Inlyta treatmentDrug

    Combined Sintilimab injection and Inlyta treatment in FH-deficient RCC

Study groups in NCT04387500
Study groupRoleWhat they receive
Sintilimab injection combined with InlytaExperimentalSintilimab 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.
Receives: Drug: Sintilimab injection plus Inlyta treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR

    objective response rate

    Measured: 3 years

  2. PFS

    progression-free survival

    Measured: 3 years

Secondary outcomes (6)

  1. OS

    overall survival

    Measured: 3 years

  2. EQ-5D-5L

    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.

    Measured: Up to 36 months

  3. FKSI-19

    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.

    Measured: Up to 36 months

  4. DCR

    Disease control rate

    Measured: 3 years

  5. Duration of response

    time from the first occurrence of treatment response (CR or PR) to disease progression or death

    Measured: 3 years

  6. VAS

    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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2020
  2. Study start1 Jul 2021
  3. Primary completion1 Mar 2025 (estimated)
  4. Study completion1 Jan 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04387500
Sponsor's protocol ID
20190813
Status last verified
Apr 2024
First submitted
15 Aug 2019
Last updated
9 Apr 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: There is a plan to make IPD and related data dictionaries available.

Publications

  • 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, Aittomaki 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. doi: 10.1038/ng849. Epub 2002 Feb 25.

    PubMed 11865300

  • 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. doi: 10.1016/j.ccr.2005.06.017.

    PubMed 16098467

  • 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.

    PubMed 22101431

  • 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, Molinie 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.

    PubMed 22014576

  • 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.

    PubMed 27601542

  • Kusmartsev S, Eruslanov E, Kubler 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. doi: 10.4049/jimmunol.181.1.346.

    PubMed 18566400

  • Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Canamero 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.

    PubMed 27571927

  • 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 IL1beta, IL8, CXCL5, and Mip-1alpha. Clin Cancer Res. 2017 May 1;23(9):2346-2355. doi: 10.1158/1078-0432.CCR-15-1823. Epub 2016 Oct 31.

    PubMed 27799249

  • Zhang X, Liu H, Zhang Y, et al. Phase II, multi-center study of sintilimab in combination with axitinib in patient with advanced fumarate hydratase-deficient renal cell carcinoma. Presented at: 2023 AUA Annual Meeting; April 28-May 1, 2023; Chicago, IL. Abstract PD24-09.

  • Zhang X, Liu H, Liang J, Zhao J, Wang Y, Chen Y, Kang D, Chen Q, Zhang Y, Yin X, Zeng Y, Wang Z, Sheng X, Yao X, Gong K, Liu X, Chen Z, Qiu M, Chen W, Wang Z, Luo G, Zhou T, Yang N, Pan X, Nie L, Zhang M, Chen J, Zhao J, Hu X, Xu L, Tang B, Dai J, Liu H, Ni Y, Huang R, Wei Q, Li X, He Q, Liu J, Shen P, Chen N, Liu Z, Sun G, Yao J, Zeng H. Sintilimab Plus Axitinib for Advanced Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 Oct 1;11(10):1169-1177. doi: 10.1001/jamaoncol.2025.2497.

    PubMed 40810951

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sintilimab injection plus Inlyta treatment in people with Carcinoma, Renal Cell and Fumarate Hydratase Deficiency, run by West China Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04387500, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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