Endometrial CancerEarly Phase 1NCT03694834
Window of Opportunity Pilot Study of Pembrolizumab in Obesity-driven Endometrial Cancer
A Early Phase 1 study testing Pembrolizumab and Hysterectomy in people with Endometrial Cancer and Uterine Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
Programmed cell death 1 (PD-1) inhibitor treatment may benefit patients with endometrial cancer (EC) based on the following observations: 1) an overwhelming presence of PD-1 in ECs; 2) the well-known effect of obesity which activates pro-inflammatory white blood cells and promotes the development of ECs; and 3) the… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer, Uterine Cancer
- What is being tested?
- Pembrolizumab and Hysterectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2019to 23 Oct 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Female Age ≥ 18 years at the time of consent.
- ECOG Performance Status of ≤ 1 (See Appendix 11.4).
- Diagnosis of advanced stage and histologically confirmed endometrioid, serous, clear cell, carcinosarcoma (including mixed) cancer of the uterus in which neoadjuvant chemotherapy is planned.
- Has received no prior therapy for uterine cancer, including hysterectomy
- Subjects 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.
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- Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.
- Have an available endometrial biopsy for correlative studies and willing to undergo a research biopsy prior to initiating study treatment. The research biopsy procedure must be deemed medically safe by the investigator.
- Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Who cannot join
- Active infection requiring systemic therapy.
- Pregnant or breastfeeding
- Has received a live vaccine within 30 days prior to the first dose of study drug.
- Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Subject is receiving prohibited medications or treatments that cannot be discontinued/replaced by an alternative therapy.
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- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen; HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has a history of symptomatic congestive heart failure (e.g. congestive heart failure defined as New York Heart Association (NYHA) Class III or IV functional status), unstable angina pectoris or cardiac arrhythmia.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
About this study
Programmed cell death 1 (PD-1) inhibitor treatment may benefit patients with endometrial cancer (EC) based on the following observations: 1) an overwhelming presence of PD-1 in ECs; 2) the well-known effect of obesity which activates pro-inflammatory white blood cells and promotes the development of ECs; and 3) the high prevalence of a specific gene pattern (ie, microsatellite instability hypermutated [MSI high]) among ECs that may be particularly sensitive to this class of drugs. To identify potential biomarkers of response to PD-1 inhibitors in EC, we will conduct a window of opportunity study of pembrolizumab in 20 patients with clinical stage 1, grade 3 EC, encompassing endometrioid, serous and clear cell histologies. Eligible patients will undergo a research biopsy for collection of fresh tissue at the time of enrollment, in addition to the routinely performed endometrial biopsy that led to the diagnosis of their cancer. Patients will receive a single dose of pembrolizumab (200 mg IV) prior to undergoing their scheduled hysterectomy with surgical staging three weeks later. As per standard of care, adjuvant chemotherapy with paclitaxel and carboplatin will be recommended after hysterectomy/surgical staging for women with endometrioid tumors and stage III disease or women with serous/clear cell tumors at all stages of disease. However, in this study pembrolizumab will be added to adjuvant paclitaxel and carboplatin for EC. Pre-treatment endometrial biopsy specimens (fresh frozen tissue and formalin-fixed paraffin embedded (FFPE)) and a post-treatment hysterectomy specimen (fresh frozen tissue and FFPE) will be collected for translational studies. Blood, fecal and vaginal samples will be collected pre-treatment, at the time of surgery and following 3 cycles of adjuvant pembrolizumab/paclitaxel/carboplatin treatment.
Read the detailed description
The primary objective of the trial is to measure the change in number and phenotype of tumor-infiltrating lymphocytes, including delineation of effector and regulatory T cells, before and after one cycle of pembrolizumab treatment. Other correlative secondary objectives include investigation of associations among pre-treatment TIL numbers, clonality of TILs and change in number and phenotype of TILs with samples collected after pembrolizumab treatment between MSI and DNA polymerase (POLE) ultramutated ECs versus MSI low/stable ECs versus copy number high (CNH) ECs, among others. To assess the complex interplay between obesity, molecular subtype, the microbiome and immune regulation, gut, vaginal and uterine microbiota profiles will be characterized and potential associations with body mass index (BMI), pre-treatment TIL numbers, clonality of TILs and change in the number and phenotype of TILs will be investigated. Secondary clinical objectives include (1) of the pathologic response rate after one cycle of pembrolizumab following hysterectomy and surgical staging in stage I/II, serous/clear cell EC and stage III, G3 (serous, clear cell or endometrioid histologies) EC and (2) characterization of the toxicity profile of pembrolizumab pre-hysterectomy and in combination with paclitaxel and carboplatin as adjuvant therapy for EC.
- Conditions
- Endometrial Cancer, Uterine Cancer
- Being tested
- Pembrolizumab, Hysterectomy
- Keywords
- Endometrial Cancer, Uterus, Endometrioid
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
A single dose of Pembrolizumab (200 mg) will be administered IV over 30 min (-5 /+10 min) approximately 3 weeks prior to the scheduled hysterectomy.
Pembrolizumab (200 mg) will be administered IV over 30 min (-5/+10 min) every three weeks in combination with paclitaxel and carboplatin as adjuvant therapy over 6 cycles. Pembrolizumab should be given on D1 of each cycle after the infusion of cytotoxics.
HysterectomyProcedure or surgery
Hysterectomy/Surgical Staging per institutional standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm - Pembrolizumab | Experimental | Single dose of Pembrolizumab 200mg IV administered prior to hysterectomy and surgical staging. Receives: Drug: Pembrolizumab; Procedure: Hysterectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the number of Tumor Infiltrating Lymphocytes
Change in number of tumor-infiltrating lymphocytes in response to single dose of pembrolizumab will be determined by performing histopathologic analysis of H\&E-stained tumor sections collected at baseline and at the time of surgery.
Measured: 3 weeks
Secondary outcomes (6)
Number of patients who experience Adverse Events after one dose of Pembrolizumab
The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Measured: 3 weeks
Change in number of Tumor Infiltrating Lymphocytes by endometrial cancer sub-types
Count and compare associations of (1) pre-treatment Tumor Infiltrating Lymphocyte (TIL) numbers (2) clonality of TILs and (3) change in number and phenotype of TILs with pembrolizumab treatment between Microsatellite Instability (MSI) and DNA Polymerase ε Endometrial Cancers (EC) versus MSI low/stable ECs versus Copy Number High ECs.
Measured: 3 weeks
Correlation of Programmed Cell Death-1 (PD-1) Expression with TILs
Compare possible associations of PD-1, Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) messenger Ribonucleic Acid (mRNA) expression with (1) pre-treatment TIL numbers (2) clonality of TILs and (3) change in number and phenotype of TILs.
Measured: 3 weeks
Correlation of Immune and Obesity/Inflammation EC Signatures with TILs
Compare possible associations of immune and obesity/inflammation EC signatures with (1) Body Mass Index (BMI) (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
Measured: 3 weeks
Correlation of Microbiota Profiles with TILs
Compare possible associations of gut, vaginal and uterine microbiota profiles with (1) BMI (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
Measured: 3 weeks
Overall Response Rate of Pembrolizumab with Paclitaxel and Carboplatin
Calculate the overall response rate of pembrolizumab in combination with paclitaxel and carboplatin following hysterectomy and surgical staging in (1) stage I/II, serous/clear cell EC and (2) stage III, Grade 3 (serous, clear cell or endometrioid histologies) EC.
Response is measured as:
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis <10mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2018
- Study start29 Mar 2019
- Primary completion23 Oct 2023
- Study completion23 Oct 2023
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Victoria Bae-Jump, MD, Principal investigator, UNC-Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03694834
- Sponsor's protocol ID
- LCCC 1739
- Status last verified
- Nov 2023
- First submitted
- 1 Oct 2018
- Last updated
- 28 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window of Opportunity Pilot Study of Pembrolizumab in Obesity-driven Endometrial Cancer
- ClinicalTrials.gov ID
- NCT03694834
- Acronym / sponsor ID
- LCCC 1739
- Conditions
- Endometrial Cancer, Uterine Cancer
- Keywords
- Endometrial Cancer, Uterus, Endometrioid
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 29 Mar 2019 (actual)
- Primary completion
- 23 Oct 2023 (actual)
- Study completion
- 23 Oct 2023 (actual)
- First posted
- 3 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Programmed cell death 1 (PD-1) inhibitor treatment may benefit patients with endometrial cancer (EC) based on the following observations: 1) an overwhelming presence of PD-1 in ECs; 2) the well-known effect of obesity which activates pro-inflammatory white blood cells and promotes the development of ECs; and 3) the high prevalence of a specific gene pattern (ie, microsatellite instability hypermutated [MSI high]) among ECs that may be particularly sensitive to this class of drugs. To identify potential biomarkers of response to PD-1 inhibitors in EC, we will conduct a window of opportunity study of pembrolizumab in 20 patients with clinical stage 1, grade 3 EC, encompassing endometrioid, serous and clear cell histologies. Eligible patients will undergo a research biopsy for collection of fresh tissue at the time of enrollment, in addition to the routinely performed endometrial biopsy that led to the diagnosis of their cancer. Patients will receive a single dose of pembrolizumab (200 mg IV) prior to undergoing their scheduled hysterectomy with surgical staging three weeks later. As per standard of care, adjuvant chemotherapy with paclitaxel and carboplatin will be recommended after hysterectomy/surgical staging for women with endometrioid tumors and stage III disease or women with serous/clear cell tumors at all stages of disease. However, in this study pembrolizumab will be added to adjuvant paclitaxel and carboplatin for EC. Pre-treatment endometrial biopsy specimens (fresh frozen tissue and formalin-fixed paraffin embedded (FFPE)) and a post-treatment hysterectomy specimen (fresh frozen tissue and FFPE) will be collected for translational studies. Blood, fecal and vaginal samples will be collected pre-treatment, at the time of surgery and following 3 cycles of adjuvant pembrolizumab/paclitaxel/carboplatin treatment.
Detailed description
The primary objective of the trial is to measure the change in number and phenotype of tumor-infiltrating lymphocytes, including delineation of effector and regulatory T cells, before and after one cycle of pembrolizumab treatment. Other correlative secondary objectives include investigation of associations among pre-treatment TIL numbers, clonality of TILs and change in number and phenotype of TILs with samples collected after pembrolizumab treatment between MSI and DNA polymerase (POLE) ultramutated ECs versus MSI low/stable ECs versus copy number high (CNH) ECs, among others. To assess the complex interplay between obesity, molecular subtype, the microbiome and immune regulation, gut, vaginal and uterine microbiota profiles will be characterized and potential associations with body mass index (BMI), pre-treatment TIL numbers, clonality of TILs and change in the number and phenotype of TILs will be investigated. Secondary clinical objectives include (1) of the pathologic response rate after one cycle of pembrolizumab following hysterectomy and surgical staging in stage I/II, serous/clear cell EC and stage III, G3 (serous, clear cell or endometrioid histologies) EC and (2) characterization of the toxicity profile of pembrolizumab pre-hysterectomy and in combination with paclitaxel and carboplatin as adjuvant therapy for EC.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm - Pembrolizumab | Experimental | Drug: Pembrolizumab, Procedure: HysterectomySingle dose of Pembrolizumab 200mg IV administered prior to hysterectomy and surgical staging. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
- Female Age ≥ 18 years at the time of consent.
- ECOG Performance Status of ≤ 1 (See Appendix 11.4).
- Diagnosis of advanced stage and histologically confirmed endometrioid, serous, clear cell, carcinosarcoma (including mixed) cancer of the uterus in which neoadjuvant chemotherapy is planned.
- Has received no prior therapy for uterine cancer, including hysterectomy
Key exclusion criteria (16 listed)
- Active infection requiring systemic therapy.
- Pregnant or breastfeeding
- Has received a live vaccine within 30 days prior to the first dose of study drug.
- Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaA single dose of Pembrolizumab (200 mg) will be administered IV over 30 min (-5 /+10 min) approximately 3 weeks prior to the scheduled hysterectomy. Pembrolizumab (200 mg) will be administered IV over 30 min (-5/+10 min) every three weeks in combination with paclitaxel and carboplatin as adjuvant therapy over 6 cycles. Pembrolizumab should be given on D1 of each cycle after the infusion of cytotoxics. | Drug | Single Arm - Pembrolizumab |
| HysterectomyHysterectomy/Surgical Staging per institutional standard of care. | Procedure or surgery | Single Arm - Pembrolizumab |
Primary outcome
Change in the number of Tumor Infiltrating Lymphocytes
Time frame: 3 weeks
Change in number of tumor-infiltrating lymphocytes in response to single dose of pembrolizumab will be determined by performing histopathologic analysis of H\&E-stained tumor sections collected at baseline and at the time of surgery.
6 secondary outcomes
Number of patients who experience Adverse Events after one dose of Pembrolizumab
Time frame: 3 weeks
Change in number of Tumor Infiltrating Lymphocytes by endometrial cancer sub-types
Time frame: 3 weeks
Correlation of Programmed Cell Death-1 (PD-1) Expression with TILs
Time frame: 3 weeks
Correlation of Immune and Obesity/Inflammation EC Signatures with TILs
Time frame: 3 weeks
Correlation of Microbiota Profiles with TILs
Time frame: 3 weeks
Overall Response Rate of Pembrolizumab with Paclitaxel and Carboplatin
Time frame: 3 weeks
Results and safety
The study was stopped early (reason given: Slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- UNC Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoria Bae-Jump, MD principal investigator
UNC-Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pembrolizumab and Hysterectomy in people with Endometrial Cancer and Uterine Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the number of Tumor Infiltrating Lymphocytes (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.