A Phase III Randomized Trial of Radiation +/- Pembrolizumab (MK-3475) for Newly Diagnosed Early Stage High Intermediate Risk Mismatch Repair Deficient (dMMR) Endometrioid Endometrial Cancer

Plain English Summary

Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to the Usual Radiation Treatment for Newly Diagnosed Early Stage High Intermediate Risk Endometrial Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Endometrial Endometrioid Adenocarcinoma, Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, Stage II Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8. Tests if adding Pembrolizumab to radiation therapy can reduce cancer recurrence in early stage endometrial cancer patients. For patients with newly diagnosed stage I-II endometrial cancer who are at high intermediate risk. Participation involves undergoing radiation therapy and possibly Pembrolizumab, with regular check-ups and blood tests. Alternative treatments include standard radiation therapy alone. The trial aims to enroll 164 participants.

Official Summary

This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if age >= 18, newly diagnosed stage I-II endometrial cancer, and deficient mismatch repair. Not eligible if previously treated for endometrial cancer or have active autoimmune diseases. Age range: 18-120, with specific risk factor criteria based on age. Health requirements: normal blood counts, liver and kidney function. This trial is studying Endometrial Endometrioid Adenocarcinoma, Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, Stage II Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the 3-year recurrence-free survival, indicating how well the treatment prevents cancer from coming back. The specific primary outcome measures are: 3 year recurrence-free survival (Time from study entry (randomization) to the time of withdrawal, death, or cancer recurrence, assessed at 3 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill the gap in treatment options for high-risk early stage endometrial cancer patients, potentially offering a more effective approach to prevent cancer recurrence. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Endometrial Endometrioid Adenocarcinoma, Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, Stage II Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8, where improved treatment options are needed.

Investor Insight

The market size for endometrial cancer treatments is significant, with this trial positioning itself as a competitive player in the field of immunotherapy for gynecological cancers. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your risk factors and whether you meet the eligibility criteria. Participation involves regular check-ups, blood tests, and possibly receiving Pembrolizumab and radiation therapy. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 164 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood
• RADIATION: Brachytherapy — Undergo vaginal brachytherapy
• PROCEDURE: Computed Tomography — Undergo CT
• RADIATION: External Beam Radiation Therapy — Undergo EBRT
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI

Primary Outcomes

• 3 year recurrence-free survival (Time from study entry (randomization) to the time of withdrawal, death, or cancer recurrence, assessed at 3 years)

Secondary Outcomes

• Incidence of adverse events (12 months)
• Recurrence patterns (5 years)
• 5 year recurrence free survival (Time from study entry (randomization) to the time of cancer recurrence, assessed at 5 years)
• Overall survival (Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years)
• Patient-reported outcomes (Up to 2 years after starting treatment)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have:

  * Stage I endometrioid endometrial cancer and a combination of age and risk factors as listed below:

    * Age \>= 70 and 1 or more risk factors
    * Age 50 - \< 70 and 2 or more risk factors
    * Age \< 50 and 3 risk factors

      * Risk factors:

        * Myometrial invasion \>= 50%
        * Lymphovascular space invasion
        * Grade 2 or 3 OR
  * Stage II endometrioid endometrial cancer

    * Note: Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes
* CT or MRI abdomen or pelvis and either chest X-ray or CT chest demonstrating no evidence of disease outside of the uterus. Imaging can be performed pre-operatively or post-operatively. CT with contrast is the preferred modality. Positron emission tomography (PET)/CT is NOT to be used for any disease assessment or reassessment unless there is documentation that PET/CT is of diagnostic quality equal to CT with contrast
* Patients must have deficient mismatch repair as demonstrated by lack of expression of at least one mismatch repair protein by immunohistochemistry (IHC) and/or evidence of microsatellite instability (MSI) high. The institutional pathology report documenting MMR deficiency must be submitted
* Patients must have undergone surgical staging with at least hysterectomy, removal of cervix, bilateral (if both are present) salpingo-oophorectomy, and either sentinel lymph node assessment or complete pelvic +/- aortic lymphadenectomy. Secondary staging is allowed to determine stage. Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes
* Patients must have received no prior therapy for endometrial cancer, including hormonal therapy, chemotherapy, targeted therapy, immunotherapy or radiation therapy
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Platelets \>= 100,000/mcl (within 14 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1,500/mcl (within 14 days prior to registration)
* Creatinine =\< 1.5 x laboratory upper limit of normal (ULN) (within 14 days prior to registration)
* Bilirubin =\< 1.5 x ULN (within 14 days prior to registration) (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (within 14 days prior to registration)
* Thyroid stimulating hormone (TSH) within normal limits (TSH \< ULN allowed in euthyroid patients on thyroid replacement therapy)
* Patients must be registered between 1 and 8 weeks after initial (staging) surgery performed for the combined purpose of diagnosis and staging
* 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
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

* Patients who are currently participating and receiving cancer-directed study therapy for endometrial cancer or have participated in a study of an investigational agent and received cancer-directed study therapy for endometrial cancer within 4 weeks prior to registration
* Patients who have received prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or other similar agents
* Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or MK-3475 (pembrolizumab) and/or its excipients
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyr

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Community Cancer Institute, Clovis, California, United States
• University Oncology Associates, Clovis, California, United States
• John Muir Medical Center-Concord, Concord, California, United States
• UC San Diego Moores Cancer Center, La Jolla, California, United States
• Los Angeles General Medical Center, Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
• UCLA / Jonsson Comprehensive Cancer Center, Los Angeles, California, United States
• UCSF Medical Center-Mission Bay, San Francisco, California, United States
• John Muir Medical Center-Walnut Creek, Walnut Creek, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Related conditions include other types of endometrial cancer, as well as other gynecological cancers such as ovarian and cervical cancer.
• Therapeutic areas include immunotherapy, radiation therapy, and surgical treatment for gynecological malignancies.

More Endometrial Endometrioid Adenocarcinoma Trials

View all Endometrial Endometrioid Adenocarcinoma clinical trials