- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04906382
Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer
Pilot Study of Tislelizumab (BGB-A317) in Recurrent Mismatch Repair Deficient Endometrial Cancer and the Effect on the Tumor Microenvironment
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. 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:
I. 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:
I. 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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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)
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (tislelizumab)
Chemo 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. |
Given IV
Other Names:
Given IV
Other Names:
Undergo biopsy
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
T-cell receptor (TCR) profiles
Time Frame: Up to 24 months
|
1) Measurements of TCRB clonal expansion in peripheral blood.
Measurements of TCR in peripheral blood/-tissue
|
Up to 24 months
|
T-cell receptor (TCR) clonality
Time Frame: Up 24 month
|
Measurements of TCRB clonal expansion in peripheral blood.
|
Up 24 month
|
T-cell receptor (TCR) diversity
Time Frame: Up to 24 months
|
Measurements of TCRB diversity in peripheral blood
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Up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor mutational profiles
Time Frame: Up to 3 years
|
Evaluated using whole exome sequencing
|
Up to 3 years
|
PD-L1 expression and other immune markers in tissue
Time Frame: up to 24 weeks
|
Evaluated using immunohistochemistry
|
up to 24 weeks
|
Overall response rate (objective response rate complete response [CR] and partial response [PR]; clinical benefit rate CR + PR + stable)
Time Frame: Up to 3 years
|
Evaluated by Response Evaluation Criteria in Solid Tumors version 1.1.
|
Up to 3 years
|
Progression-free survival
Time Frame: From date of enrollment to date of progressive disease, assessed up to 5 years
|
Estimated using Kaplan-Meier method.
|
From date of enrollment to date of progressive disease, assessed up to 5 years
|
Overall survival
Time Frame: Up to 5 years
|
Estimated using Kaplan-Meier method.
|
Up to 5 years
|
Incidence of adverse events
Time Frame: Up to 2 years
|
Assessed using CTCAE v5.0
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Floor Backes, MD, Ohio State University Comprehensive Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
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
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Metabolic Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Diseases
- Disease Attributes
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Genetic Diseases, Inborn
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Neoplastic Syndromes, Hereditary
- DNA Repair-Deficiency Disorders
- Neoplasms, Complex and Mixed
- Sarcoma
- Recurrence
- Colorectal Neoplasms, Hereditary Nonpolyposis
- Endometrial Neoplasms
- Carcinosarcoma
- Mixed Tumor, Mullerian
- Adenocarcinoma, Clear Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Carboplatin
- Paclitaxel
- Albumin-Bound Paclitaxel
Other Study ID Numbers
- OSU-20173
- NCI-2021-01367 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
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