Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT03914612|
Recruitment Status : Recruiting
First Posted : April 15, 2019
Last Update Posted : September 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Clear Cell Adenocarcinoma 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 Endometrioid Adenocarcinoma Recurrent Endometrial Mixed Cell Adenocarcinoma Recurrent Endometrial Serous Adenocarcinoma Recurrent Endometrial Undifferentiated Carcinoma Stage III Uterine Corpus Cancer AJCC v8 Stage IIIA Uterine Corpus Cancer AJCC v8 Stage IIIB Uterine Corpus Cancer AJCC v8 Stage IIIC Uterine Corpus Cancer AJCC v8 Stage IIIC1 Uterine Corpus Cancer AJCC v8 Stage IIIC2 Uterine Corpus Cancer AJCC v8 Stage IV Uterine Corpus Cancer AJCC v8 Stage IVA Uterine Corpus Cancer AJCC v8 Stage IVB Uterine Corpus Cancer AJCC v8||Drug: Carboplatin Drug: Paclitaxel Biological: Pembrolizumab Other: Placebo Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||810 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||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|
|Actual Study Start Date :||July 16, 2019|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2023|
Active Comparator: Arm I (placebo, paclitaxel, carboplatin)
COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients with SD or PR who still have measurable disease receive placebo IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Experimental: Arm II (pembrolizumab, paclitaxel, carboplatin)
COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients with SD or PR who still have measurable disease receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Progression-free survival (PFS) [ Time Frame: Duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years ]Will be tested with a stratified log-rank statistic.
- Incidence of adverse events [ Time Frame: 5 years ]Assessed by Common Terminology Criteria for Adverse Events (CTCAE). Toxicities will be screened for differences between treatments by using an exact method or a Chi-Square test. For a given adverse event, each patient will be graded according to the worse grade experienced while on therapy (and within 30 days of treatment). These toxicities will then be divided into two or three categories such as mild, moderate, and severe or mild to moderate versus severe. The rates of severe toxicities may be characterized by risk ratios or odds ratios with confidence intervals (unadjusted for multiplicity). The number of toxicities examined is usually fairly large, so these analyses will be considered exploratory and may be inspected in light of other studies.
- Objective tumor response [ Time Frame: 5 years ]Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.
- Duration of objective response [ Time Frame: 5 years ]The time difference between the dates of first response and first progression; patients who do not progress are considered censored.
- Overall survival (OS) [ Time Frame: Time from study entry to time of death or the date of last contact, assessed up to 5 years ]
- Quality of life (QoL) and patient-reported outcomes (PROs) [ Time Frame: 5 years ]Measured by the Function Assessment of Cancer Therapy (FACT)-Endometrial Trial Outcome Index (En-TOI), the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (short), Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue (short form),the PROMIS-physical function (short form) and a single-item measuring bother from side effects of cancer therapy. A linear mixed model for repeated measures will be used to estimate and compare the mean differences between the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, pre-treatment quality of life/patient reported outcome score, assessment time and treatment-by-time interaction. The stratification factors will be the same factors included in the clinical primary analysis. Hochberg's step-up multiple testing procedure (Hochberg, 1988) will be used to adjust p-values for each assessment time points estimated from the fitted model.
- Incidence of pembrolizumab treatment and self-reported neurotoxicity [ Time Frame: 5 years ]Assessed with FACT/GOG-Ntx.
- Concordance between Institutional Mismatch repair (MMR) immunohistochemistry (IHC) testing and centralized MMR IHC [ Time Frame: 5 years ]Concordance between institutional MMR IHC testing and centralized MMR IHC. The patient's MMR status will be assessed for prognostic value by conducting stratified log-rank tests or Cox Proportional Hazards (PH) modeling when assessing the impact on PFS or OS. When assessing the impact on the probability of response, a logistic regression model will be considered and include other pertinent variables that may influence response. A Cox PH model will be used to assess predictive value of MMR status for regimen efficacy through an interaction term. A similar type of analysis may be attempted with response using logistic regression. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
- Effect of pembrolizumab on PFS and OS by PD-L1 IHC [ Time Frame: 5 years ]Will assess the effect of pembrolizumab on PFS and OS by PD-L1 IHC (combined positive score [CPS]) within proficient MMR (pMMR) and deficient MMR (dMMR) populations. The effectiveness of pembrolizumab will be compared by PD-L1 status (CPS). A formal test will be conducted by examining the interaction term between pembrolizumab treatment (yes or no) with PD-L1 status. The association between PD-L1 CPS status and MMR status will be assessed with odds ratios. A test may be conducted with a Fisher's Exact Test, and confidence intervals will be provided.
- Association between Program Death Ligand 1 (PD-L1) IHC and MMR status [ Time Frame: 5 years ]Measures of association between PD-L1 IHC (CPS) and MMR status. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03914612
|United States, Alabama|
|University of Alabama at Birmingham Cancer Center||Recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: Site Public Contact 205-934-0220 email@example.com|
|Principal Investigator: Charles A. Leath|
|United States, Alaska|
|Alaska Women's Cancer Care||Recruiting|
|Anchorage, Alaska, United States, 99508|
|Contact: Site Public Contact 907-212-6871 AKPAMC.OncologyResearchSupport@providence.org|
|Principal Investigator: Dan S. Zuckerman|
|United States, Illinois|
|University of Illinois||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Site Public Contact 312-355-3046|
|Principal Investigator: Shannon MacLaughlan|
|Springfield, Illinois, United States, 62702|
|Contact: Site Public Contact 800-444-7541|
|Principal Investigator: Bryan A. Faller|
|United States, Maryland|
|Greater Baltimore Medical Center||Recruiting|
|Baltimore, Maryland, United States, 21204|
|Contact: Site Public Contact 443-849-3706|
|Principal Investigator: Kimberly L. Levinson|
|United States, Missouri|
|Saint Luke's Hospital of Kansas City||Recruiting|
|Kansas City, Missouri, United States, 64111|
|Contact: Site Public Contact 913-948-5588 firstname.lastname@example.org|
|Principal Investigator: Michelle Rowland|
|United States, Ohio|
|Good Samaritan Hospital - Cincinnati||Recruiting|
|Cincinnati, Ohio, United States, 45220|
|Contact: Site Public Contact 308-398-6518 email@example.com|
|Principal Investigator: Richard L. Deming|
|ProMedica Flower Hospital||Recruiting|
|Sylvania, Ohio, United States, 43560|
|Contact: Site Public Contact 419-824-1842|
|Principal Investigator: Adam C. Walter|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Site Public Contact 405-271-8777 firstname.lastname@example.org|
|Principal Investigator: Lisa M. Landrum|
|United States, Rhode Island|
|Women and Infants Hospital||Recruiting|
|Providence, Rhode Island, United States, 02905|
|Contact: Site Public Contact 401-274-1122|
|Principal Investigator: Cara A. Mathews|
|United States, South Dakota|
|Avera Cancer Institute||Recruiting|
|Sioux Falls, South Dakota, United States, 57105|
|Contact: Site Public Contact 888-634-7268 email@example.com|
|Principal Investigator: David C. Starks|
|United States, West Virginia|
|Morgantown, West Virginia, United States, 26505|
|Contact: Site Public Contact 304-598-6560|
|Principal Investigator: William C. McBee|
|Principal Investigator:||Ramez N Eskander||NRG Oncology|