The main goal of this clinical trial is to evaluate dostarlimab, an immunotherapy drug, as a potential alternative to surgery for early-stage endometrial cancer with Mismatch Repair deficiency, a genetic cause for 20-30% of cases. The study aims to establish dostarlimab's efficacy and safety in early-stage endometrial cancer, exploring its potential as a non surgical option for those unsuitable or unwilling to undergo major surgery, allowing for fertility preservation or addressing specific health conditions. Participants will have seven dostarlimab sessions over 12 months. The treatment plan involves four cycles every three weeks, followed by a three-week break, and then three cycles every six weeks. This research is a promising step toward a new, less invasive treatment choice for patients with specific genetic traits. It expands the range of care options for endometrial cancer.
Cancer of the endometrium is a common type of cancer that affects over 3,000 women in Australia every year. The usual way to treat this cancer is by having surgery to remove the uterus, fallopian tubes, ovaries, and sometimes lymph nodes. But this surgery might not be the best choice for women who want to have children or for older women, those with obesity, or people with other health problems, because surgery can be risky for them. Big improvements in the treatment of endometrial cancer have occurred due to new technology and enhanced understanding of this cancer. In the past, doctors decided how to treat this cancer based on what it looked like and how likely it was to come back. But in recent years, they've been looking at the genes of the cancer to figure out the best treatment for each person. This is important to make sure each patient gets the right care. The research project evaluates dostarlimab, an immunotherapy drug, as a potential alternative to surgery for early-stage endometrial cancer with Mismatch Repair deficiency, a genetic cause for 20-30% of cases. DNA repair errors can lead to cancer, and the Mismatch Repair (MMR) pathway addresses these errors. dostarlimab enhances the immune system's ability to combat cancer by blocking specific proteins, and while approved in Australia for advanced cases, its effectiveness in early-stage cancer is unknown. The study aims to establish dostarlimab's efficacy and safety in early-stage endometrial cancer, exploring its potential as a non-surgical option for those unsuitable or unwilling to undergo major surgery, allowing for fertility preservation or addressing specific health conditions. The study proposes a unique approach to endometrial cancer treatment. Participation involves seven dostarlimab sessions over 12 months, with a treatment protocol of four cycles every three weeks, followed by a three-week break, and then three cycles every six weeks. Dostarlimab is approved in Australia for the treatment of adult patients with recurrent or advanced mismatch repair deficient endometrial cancer. However, it is not currently approved to treat early-stage endometrial cancer. This study will test to see if dostarlimab is an effective treatment for early-stage mismatch repair deficient endometrial cancer. Dostarlimab may be a good option for women who cannot or do not want to have surgery to remove their uterus, fallopian tubes, ovaries and lymph nodes, or who want to keep the option of having children. This research offers hope for a novel, non-invasive treatment option for patients with specific genetic characteristics, expanding the scope of endometrial cancer care. Primary objective: To determine the absence of endometrial cancer following protocol treatment regimen of dostarlimab Secondary objective: To determine the safety and tolerability of dostarlimab in participants with early-stage MMR deficient endometrioid endometrial adenocarcinoma Exploratory Objective: * To assess study feasibility * Assess participant evaluation of study participation providing consumer feedback to inform future clinical research programs. * To assess longer term (9 and 12 months) changes to laboratory and clinical parameters post treatment with dostarlimab. * Exploratory investigations utilizing biobanked tissue, blood samples for participant treated with dostarlimab. * An exploratory outcome of increased clinical efficacy (pCR) related to irAEs. * Fertility Outcome
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
The dosing regimen follows standard clinical care protocol comprising of 4 cycles every 3-weeks, a rest period of 34 weeks followed by 3 cycles every 6 weekly for a total of 7 cycles.
Westmead Hospital
Sydney, New South Wales, Australia
NOT_YET_RECRUITINGRoyal Brisbane and Women's Hospital
Brisbane, Queensland, Australia
RECRUITINGPeter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGDetermine the absence endometrial cancer following protocol treatment regimen of dostarlimab.
Number of participants achieving investigator-assessed pathological complete response (pCR).
Time frame: Week 27 (Month 6)
Determine the safety and tolerability of dostarlimab in participants with early-stage MMR deficient endometrioid endometrial adenocarcinoma.
Safety analyses including incidence of treatment-emergent adverse events (TEAEs), immune-related AEs of interest (irAEIs), and serious adverse events (SAEs), toxicities graded 3-5 as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0).
Time frame: From Cycle 1 /Day 1 to 30 days post last dose, 9 and 12months.
TEAEs/irAEIs Leading to Study Drug Discontinuation
Explore the frequency and severity of TEAEs/irAEIs that lead to discontinuation of the study drug.
Time frame: Screening to Cycle 7 (Week 25)
TEAEs/irAEIs Leading to Study Withdrawal
Investigate and assess the frequency and severity of TEAEs/irAEIs resulting in the withdrawal of participants from the study.
Time frame: From Screening to Week 27 (6 months) 9 and 12months.
Clinically Significant Changes in Haematology
Assess the number of participants with clinically significant changes in Haematology
Time frame: From Screening to Week 27 (6 months) 9 and 12months to End of Study.
Clinically Significant Changes in Clinical Chemistry
Assess the number of participants with clinically significant changes in Clinical Chemistry
Time frame: From Screening to Week 27 (6 months) 9 and 12months to End of Study.
Clinically Significant Changes in Thyroid Function
Assess the number of participants with clinically significant changes in Thyroid Function (Measure thyroid-stimulating hormone (TSH), free thyroxine (FT4), and triiodothyronine (T3) levels.)
Time frame: From Screening to Week 27 (6 months)
Abnormal Vital Signs
Assess the number of participants with abnormal vital signs pre and post treatment.
Time frame: From Screening to Week 27 (6 months) 9 and 12months.
Abnormal Electrocardiogram (ECG) Parameters
Asses the number of participants with abnormal ECG parameters.
Time frame: Screening, Week 12 (3 months) and Week 27 (6 months)
Clinically Significant Abnormal Physical Examination
Assess the number of participants with clinically significant abnormal physical examinations.
Time frame: From screening visit to Week 27 (6 months), 9 and 12 months
Concomitant Medications
Assess the number of participants who are taking concomitant medications
Time frame: From Screening to 12 months.
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