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Lynch SyndromeEarly Phase 1NCT04906382

Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer

A Early Phase 1 study testing Biopsy, Carboplatin and Paclitaxel in people with Lynch Syndrome and Recurrent Endometrial Carcinoma, run by Floor Backes, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This clinical trial evaluates the effect of tislelizumab in treating patients with mismatch repair deficient endometrial cancer that has come back (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing DNA errors and damage. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biopsy, Carboplatin and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
1 Jul 2021to 1 Sep 2022
Phase
Early Phase 1
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
  • Age >= 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place)
  • All patients with recurrent endometrial carcinoma, of any histology including clear cell, serous papillary carcinomas, and carcinosarcoma, whose disease is not amenable to definitive local therapy (including surgery and/or radiation therapy)
  • Patients must have deficient mismatch repair as demonstrated by lack of expression of at least 1 mismatch repair protein by immunohistochemistry, or evidence of microsatellite instability (MSI) high, or evidence of Lynch syndrome
  • The patient must have a lesion that is amenable to safe biopsy and the patient must agree to pre-and post-treatment biopsies
  • Patients may have received radiation for the treatment of endometrial cancer
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  • Patient must have recovered from toxicity related to prior treatment to grade 2 or less
  • At least two weeks should have elapsed since completion of prior chemotherapy or 5 half-lives (whichever is shorter), or 4 weeks from radiation involving the whole pelvis or over 50% of the spine
  • At least 1 measurable lesion as defined per RECIST v1.1 that is amenable to biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (must not have required a blood transfusion or growth factor support =< 14 days before sample collection at screening) (during screening or =< 14 days prior to first dose of study drug)
  • Platelets >= 75 x 10^9/L (must not have required a blood transfusion or growth factor support =< 14 days before sample collection at screening) (during screening or =< 14 days prior to first dose of study drug)
  • Hemoglobin >= 9.0 g/dL (must not have required a blood transfusion or growth factor support =< 14 days before sample collection at screening) (during screening or =< 14 days prior to first dose of study drug)
  • Serum creatinine =< 1.5 x ULN (upper limit of normal) or estimated glomerular filtration rate >= 30 mL/min/1.73 m^2 by Chronic Kidney Disease Epidemiology Collaboration equation (during screening or =< 14 days prior to first dose of study drug)
  • Serum total bilirubin =< 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome) (during screening or =< 14 days prior to first dose of study drug)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (during screening or =< 14 days prior to first dose of study drug)
  • Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and >= 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test =< 7 days of first dose of study drug

Who cannot join

  • Prior therapies targeting PD-1 or PD-L1
  • Patients with symptomatic pleural effusion are excluded
  • Active leptomeningeal disease or uncontrolled brain metastasis.
  • Following treatment, these patients may then be eligible, provided all other criteria, including those for patients with a history of brain metastases, are met
  • Active autoimmune diseases or history of autoimmune diseases that may relapse.
  • Any active malignancy =< 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
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  • Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication =< 14 days before first dose of study drug
  • With uncontrolled diabetes or laboratory test abnormalities > grade 1 in potassium, sodium, or corrected calcium despite standard medical management or >= grade 3 hypoalbuminemia =< 14 days before first dose of study drug
  • With history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
  • With severe chronic or active infections (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to randomization or first dose of study drugs
  • Human immunodeficiency virus (HIV) testing is not required by protocol unless clinically indicated. Known HIV positive patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Any major surgical procedure requiring general anesthesia =< 28 days before first dose of study drug
  • Prior allogeneic stem cell transplantation or organ transplantation
  • Any of the following cardiovascular risk factors:
  • Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, =< 28 days before first dose of study drug
  • Symptomatic pulmonary embolism =< 28 days before first dose of study drug
  • Any history of acute myocardial infarction =< 6 months before first dose of study drug
  • Any history of heart failure meeting New York Heart Association (NYHA) classification III or IV =< 6 months before first dose of study drug
  • Any event of ventricular arrhythmia >= grade 2 in severity =< 6 months before first dose of study drug
  • Any history of cerebrovascular accident =< 6 months before first dose of study drug
  • Uncontrolled hypertension: systolic pressure >= 160 mmHg or diastolic pressure >= 100 mmHg despite anti-hypertension medications =< 28 days before randomization or first dose of drug
  • Any episode of syncope or seizure =< 28 days before first dose of study drug
  • A history of severe hypersensitivity reactions to tislelizumab
  • Has received any chemotherapy, immunotherapy (e.g., interleukin, interferon, thymoxin) or any investigational therapies within 14 days or 5 half-lives (whichever is shorter) of the first study drug administration
  • Has received any herbal medicine used to control cancer within 14 days of the first study drug administration
  • Was administered a live vaccine =< 4 weeks before first dose of study drug
  • Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines, and are not allowed
  • Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that, will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or result in insufficient or might impair compliance with study conduct
  • Concurrent participation in another therapeutic clinical study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Pilot Study of Tislelizumab (BGB-A317) in Recurrent Mismatch Repair Deficient Endometrial Cancer and the Effect on the Tumor Microenvironment

This clinical trial evaluates the effect of tislelizumab in treating patients with mismatch repair deficient endometrial cancer that has come back (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing DNA errors and damage. Mismatch repair deficient tumors (dMMR) may have difficulty repairing DNA mutations during replication that may affect tumor's response to therapy. Immunotherapy with monoclonal antibodies, such as tislelizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tislelizumab may help treat patients with mismatch repair deficient endometrial cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the effect of tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire in responders versus non-responders.

SECONDARY OBJECTIVES:

  1. To evaluate the effect of tislelizumab on tumor mutational profiles between responders and non-responders.

II. To evaluate the effect of tislelizumab +/- carboplatin/paclitaxel on PD-1/PD-L1 expression and other immune markers in tumor biopsies between responders and non-responders.

III. To evaluate the safety and tolerability of tislelizumab +/- carboplatin/paclitaxel in patients with MMR deficient recurrent endometrial cancer.

EXPLORATORY OBJECTIVES:

  1. To explore the effect of adding carboplatin/paclitaxel to tislelizumab on tumor mutational profiles.

II. To explore the effect of adding carboplatin/paclitaxel to tislelizumab (BGB-A317) on the diversity and dynamics of the T cell receptor repertoire.

III. To explore the objective antitumor activity (complete and partial response) of tislelizumab as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria.

IV. To explore the objective antitumor activity (complete and partial response) of tislelizumab/carboplatin/paclitaxel after single agent tislelizumab as measured by RECIST v1.1 criteria V. To explore the progression free survival in patients with mismatch repair deficiency (dMMR) recurrent endometrial cancer treated with tislelizumab +/- carboplatin/paclitaxel.

OUTLINE:

Patients receive tislelizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients who are chemotherapy naive with progressive disease, stable disease, or partial response, also receive carboplatin IV and paclitaxel IV every 21 days per standard of care for 6-9 cycles at the discretion of the treating physician.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then periodically thereafter.

Being tested
Biopsy, Carboplatin, Paclitaxel, Tislelizumab
Medical subject headings
Colorectal Neoplasms, Hereditary Nonpolyposis, Endometrial Neoplasms, Turcot syndrome

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • TislelizumabBiological

    Also called BGB-A317

    Given IV

Study groups in NCT04906382
Study groupRoleWhat they receive
Treatment (tislelizumab)ExperimentalChemo naïve patients receive tislelizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients who are chemotherapy naive with progressive disease, stable disease, or partial response, also receive carboplatin IV and paclitaxel IV every 21 days per standard of care for 6-9 cycles at the discretion of the treating physician. Patients who have received prior chemotherapy will receive single agent tislelizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Biopsy; Drug: Carboplatin; Drug: Paclitaxel; Biological: Tislelizumab

What is being measured

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

  1. T-cell receptor (TCR) profiles

    1. Measurements of TCRB clonal expansion in peripheral blood. Measurements of TCR in peripheral blood/-tissue

    Measured: Up to 24 months

  2. T-cell receptor (TCR) clonality

    Measurements of TCRB clonal expansion in peripheral blood.

    Measured: Up 24 month

  3. T-cell receptor (TCR) diversity

    Measurements of TCRB diversity in peripheral blood

    Measured: Up to 24 months

Secondary outcomes (6)

  1. Tumor mutational profiles

    Evaluated using whole exome sequencing

    Measured: Up to 3 years

  2. PD-L1 expression and other immune markers in tissue

    Evaluated using immunohistochemistry

    Measured: up to 24 weeks

  3. Overall response rate (objective response rate complete response [CR] and partial response [PR]; clinical benefit rate CR + PR + stable)

    Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1.

    Measured: Up to 3 years

  4. Progression-free survival

    Estimated using Kaplan-Meier method.

    Measured: From date of enrollment to date of progressive disease, assessed up to 5 years

  5. Overall survival

    Estimated using Kaplan-Meier method.

    Measured: Up to 5 years

  6. Incidence of adverse events

    Assessed using CTCAE v5.0

    Measured: Up to 2 years

Timeline

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

  1. First posted28 May 2021
  2. Study start1 Jul 2021
  3. Primary completion1 Sep 2022
  4. Study completion1 Sep 2022

Why it stopped: Sponsor reorganization

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04906382
Sponsor's protocol ID
OSU-20173
Other IDs
NCI-2021-01367
Status last verified
Feb 2025
First submitted
22 Mar 2021
Last updated
13 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Biopsy, Carboplatin and Paclitaxel in people with Lynch Syndrome and Recurrent Endometrial Carcinoma, run by Floor Backes, MD at 1 site in United States.

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 17 inclusion and 30 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: stopped early, as of the sponsor's last update on 13 Feb 2025. 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 United States. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this study?

The study was stopped early (reason given: Sponsor reorganization). 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?

T-cell receptor (TCR) profiles (time frame: Up to 24 months). The study lists 3 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 NCT04906382.

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 13 Feb 2025.

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