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Renal Cell CarcinomaPhase 2NCT04146831

Sintilimab in FH-deficient Renal Cell Carcinoma

A Phase 2 study testing Sintilimab in people with Renal Cell Carcinoma and FH-deficient, run by West China Hospital.

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 The sponsor has not verified this record for over two years, so it may be out of date.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, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma, FH-deficient, Sintilimab
What is being tested?
Sintilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
No sites listed yet
Study dates
1 Jun 2020to 1 Apr 2023
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

  • ≥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

Who cannot join

  • 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;
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  • 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.

About this study

Official title: Phase II Study of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma

This is a single-arm phase II clinical trial to evaluate the initial efficacy and safety of Sintilimab, a PD-1 Inhibitor, as Second-line Treatment in FH-deficient Renal Cell Carcinoma.

Read the 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.

Being tested
Sintilimab
Keywords
FH-deficient, Sintilimab, Second-line
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • SintilimabDrug

    Sintilimab: intravenous, 200mg, every 3 week. Course of treatment: Stop the treatment until clinical or radiographic progression occurs.

Study groups in NCT04146831
Study groupRoleWhat they receive
SintilimabExperimentalSintilimab is administered in this arm.
Receives: Drug: Sintilimab

What is being measured

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

  1. 6-month PFS rate (6 month progression-free survival rate)

    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).

    Measured: Up to 24 months

Secondary outcomes (9)

  1. Objective response rate (ORR)

    Complete response (CR) or partial response (PR) by Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST).

    Measured: Up to 24 months

  2. Duration of response (DOR)

    DOR is defined as the time from the date of first remission to the date of disease progression or death.

    Measured: Up to 24 months

  3. Progression-free survival (PFS)

    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).

    Measured: Up to 24 months

  4. Overall survival (OS)

    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).

    Measured: Up to 24 months

  5. Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (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 24 months

  6. Functional Assessment of Cancer Therapy- Kidney Symptom Index- Disease related Symptoms (FKSI-DRS)

    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.

    Measured: Up to 24 months

  7. EuroQol five-dimension scale (EQ-5D)

    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 24 months

  8. Visual analogue scale (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: Up to 24 months

  9. Frequency of treatment-related adverse events (AEs)

    Records were made according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 24 months

Timeline

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

  1. First posted31 Oct 2019
  2. Study start1 Jun 2020 (estimated)
  3. Primary completion1 Jun 2022 (estimated)
  4. Study completion1 Apr 2023 (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
Model description
Sintilimab
Masking
None (open label)
Enrolment
37 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04146831
Sponsor's protocol ID
CIBI30820191025
Status last verified
May 2020
First submitted
29 Oct 2019
Last updated
12 May 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sintilimab in people with Renal Cell Carcinoma and FH-deficient, run by West China Hospital.

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 15 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 12 May 2020. Status can change between updates, so confirm with the study contact before making plans.

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?

6-month PFS rate (6 month progression-free survival rate) (time frame: Up to 24 months). 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 NCT04146831.

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 12 May 2020.

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