A Phase III Randomized, Placebo-Controlled Study of Pembrolizumab (MK-3475, NSC #776864) in Addition to Paclitaxel and Carboplatin for Measurable Stage III or IVA, Stage IVB or Recurrent Endometrial Cancer

Plain English Summary

Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Recurrent Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Dedifferentiated Carcinoma. Tests if adding immunotherapy (Pembrolizumab) to standard chemotherapy (Paclitaxel and Carboplatin) improves treatment outcomes for advanced or recurrent endometrial cancer. For patients with measurable stage III-IV or recurrent endometrial cancer, including clear cell, dedifferentiated, and other types. Participation involves IV infusions of drugs and regular CT scans. Patients must be at least 18 years old and in good health. Alternatives include standard chemotherapy alone or other immunotherapy trials. The trial aims to enroll 813 participants.

Official Summary

This phase III trial studies how well the combination of pembrolizumab, paclitaxel and carboplatin works compared with paclitaxel and carboplatin alone in treating patients with endometrial cancer that is stage III or IV, or has come back after a period of improvement (recurrent). 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. Paclitaxel and carboplatin are chemotherapy drugs used as part of the usual treatment approach for this type of cancer. This study aims to assess if adding immunotherapy to these drugs is better or worse than the usual approach for treatment of this cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients have measurable endometrial cancer and have not received prior chemotherapy for this cancer. Patients must be at least 18 years old and in good health, with no other serious conditions. The trial is for advanced or recurrent endometrial cancer, including clear cell, dedifferentiated, and other types. Patients must not be pregnant and must use contraception. This trial is studying Endometrial Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Recurrent Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Dedifferentiated Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time until the cancer progresses or the patient dies, helping patients understand how well the treatment is working. The specific primary outcome measures are: Progression-free Survival (PFS) (Duration of time from study entry to time of progression per RECIST criteria or death due to any cause, whichever occurs first. The interquartile range for follow-up was (6.37 months, 30.62 months). The maximum for follow-up was 37.85 months.). 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 a treatment gap by assessing if adding immunotherapy to standard chemotherapy improves outcomes for advanced or recurrent endometrial cancer. 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 Clear Cell Adenocarcinoma, Endometrial Dedifferentiated Carcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Recurrent Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Dedifferentiated Carcinoma, where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape suggest a high approval probability for this trial, potentially leading to new treatment options for endometrial cancer patients. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 813 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if you have any of the eligible types of endometrial cancer and if you meet the age and health requirements. Participation involves IV infusions of drugs and regular CT scans. Your doctor will explain the process and any potential side effects. 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: QUADRUPLE
• Enrollment: 813 participants

Interventions

• DRUG: Carboplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT scan
• DRUG: Paclitaxel — Given IV
• BIOLOGICAL: Pembrolizumab — Given IV
• OTHER: Placebo Administration — Given IV

Primary Outcomes

• Progression-free Survival (PFS) (Duration of time from study entry to time of progression per RECIST criteria or death due to any cause, whichever occurs first. The interquartile range for follow-up was (6.37 months, 30.62 months). The maximum for follow-up was 37.85 months.)

Secondary Outcomes

• Adverse Events With Grade 3 (or Higher) (For the adverse event time frame, the interquartile range was (0.79 months, 3.42 months); the maximum was 28.39 months.)
• Objective Tumor Response (For the time frame for tumor response, the interquartile range was (2.27 months, 8.66 months) and the maximum was 36.37 months.)
• Duration of Objective Response (For the duration of objective response, the interquartile range is (4.24 months, 7.92 months); the maximum is 28.68 months.)
• Overall Survival (OS) (Time from study entry to time of death or the date of last contact, assessed up to 5 years)
• Quality of Life (QoL) in pMMR Patients Only (0-54 weeks from start of treatment)

Full Eligibility Criteria

Inclusion Criteria:

* Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
* Pathology report showing results of institutional MMR IHC testing.
* Histologic confirmation of the original primary tumor is required (submission of pathology report(s) is required). Patients with the following histologic types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.).
* Submission of tumor specimens for centralized MMR IHC testing is required after Step 1 and before Step 2 registration.
* In patients with measurable disease, lesions will be defined and monitored by RECIST version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>= 10 mm when measured by CT or magnetic resonance imaging (MRI). Lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI.
* Patients may have received

  * NO prior chemotherapy for treatment of endometrial cancer OR
  * Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\]) provided adjuvant chemotherapy was completed \>= 12 months prior to STEP 2 registration.
* Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to STEP 2 registration.
* Patients may have received prior hormonal therapy for treatment of endometrial cancer. All hormonal therapy must be discontinued at least three weeks prior to STEP 2 registration.
* Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted.
* Age \>= 18.
* Performance status of 0, 1 or 2.
* Platelets \>= 100,000/mcl.
* Absolute neutrophil count (ANC) \>= 1,500/mcl.
* Creatinine =\< 1.5 x institutional/laboratory upper limit of normal (ULN).
* Total serum bilirubin level =\< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN.
* Thyroid stimulating hormone (TSH) within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal Free T4 level is required.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 2 registration are eligible for this trial.
* For patients of child bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
* Administration of study drugs (pembrolizumab \[MK-3475\], paclitaxel, carboplatin) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from at least 14 days prior to Step 2 registration (for oral contraceptives), during treatment, and for 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Patients will be considered of nonreproductive potential if they are either:

  * Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR
  * Have a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to Step 2 registration; OR
  * Have a congenital or acquired condition that prevents childbearing.
* 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 informa

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• CTCA at Western Regional Medical Center, Goodyear, Arizona, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• Kaiser Permanente-Bellflower, Bellflower, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• Community Cancer Institute, Clovis, California, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Endometrial Clear Cell Adenocarcinoma
• Endometrial Dedifferentiated Carcinoma
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Mixed Cell Adenocarcinoma
• Endometrial Serous Adenocarcinoma
• Endometrial Undifferentiated Carcinoma
• Recurrent Endometrial Adenocarcinoma
• Recurrent Endometrial Carcinoma
• Recurrent Endometrial Clear Cell Adenocarcinoma
• Recurrent Endometrial Dedifferentiated Carcinoma

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