Endometrial CancerPhase 1NCT02630823
MK-3475 Immunotherapy in Endometrial Carcinoma
A Phase 1 study testing MK-3475 in people with Endometrial Cancer and Endometrial Carcinoma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Due to the high expression of PD-L1 in endometrial cancers as well as in ovarian cancers which are molecularly similar to uterine serous cancers, using pembrolizumab should be beneficial in this patient population. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer, Endometrial Carcinoma, Neoplasms, Endometrial
- What is being tested?
- MK-3475
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Feb 2016to 3 Oct 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of FIGO grade 3 endometrioid cancer, serous, clear cell, or mixed high grade endometrial cancer with confirmation on research-related endometrial biopsy.
- Radiographically confirmed endometrial adenocarcinoma of stages III-IV requiring adjuvant therapy. If stage III disease is suspected, there should be multiple pelvic and/or lymph nodes involved.
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1.
- Treatment plan must include primary site biopsy followed by resection of the primary tumor site and any metastatic sites at time of surgery.
- At least 18 years of age.
- GOG performance status ≤ 2
Show all 17Show fewer
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases)
- Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN
- INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
- aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants
- Sexually active women of childbearing potential must agree to contraceptive methods as described by the protocol prior to study entry, for the duration of pre-operative study participation and until definitive hysterectomy/bilateral salpingo-oophorectomy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- FIGO grade 1 or 2 endometrioid cancer.
- Radiographic imaging demonstrating uterine cancer that is probably stage I or II.
- Prior treatment for endometrial cancer.
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first dose of MK-3475 or has not recovered (i.e., to ≤ grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of MK-3475 or has not recovered (i.e., to ≤ grade 1 or baseline) from adverse events due to a previously administered agent. Note, subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note, if a subject received major surgery, she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Show all 19Show fewer
- Received a live vaccine within 30 days prior to the first dose of MK-3475. 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 (e.g. FluMist) are live attenuated vaccines and are not allowed.
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only.
- Known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of MK-3475 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of MK-3475.
- Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of MK-3475.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements.
- Has an 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 current pneumonitis.
- Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry.
- 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).
- Known history of HIV (HIV 1/2 antibodies).
- Known history of active TB.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Immunotherapy With MK-3475 in Surgically Resectable Endometrial Carcinoma
Due to the high expression of PD-L1 in endometrial cancers as well as in ovarian cancers which are molecularly similar to uterine serous cancers, using pembrolizumab should be beneficial in this patient population. Since the investigators are able to get a pre-treatment research- related endometrial biopsy as well as the surgical specimen post two cycles of pembrolizumab, the investigators will be able to evaluate the mechanism of action of this drug on the endometrial cancer tumor environment.
- Being tested
- MK-3475, Surgical resection (standard of care), Paclitaxel (standard of care), Carboplatin (standard of care), Radiation (standard of care)
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-3475Drug
Also called pembrolizumab, Keytruda
Surgical resection (standard of care)Procedure or surgery
Paclitaxel (standard of care)Drug
Also called Taxol
Carboplatin (standard of care)Drug
Also called Paraplat, Paraplatin
Radiation (standard of care)Radiation
Endometrial biopsyProcedure or surgery
Peripheral blood drawProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: MK-3475 | Experimental | * Patients will undergo endometrial biopsy followed by 2 doses of MK-3475 3 weeks apart. 3-4 weeks after the second dose of MK-3475, the standard of care surgical resection will take place, followed by standard of care adjuvant therapy. Tissue and blood will be collected at the time of surgical resection for immune analysis. For patients whose pathology confirms high-risk features and advanced stage, MK-3475 will be given every 3 weeks starting 4 -6 weeks after completion of adjuvant therapy for a maximum of 4 doses post-surgery.
* MK-3475 will be given intravenously at a dose of 200 mg over the course of 30 minutes.
* The standard of care chemotherapy will consist of 6 cycles of paclitaxel and carboplatin AUC 5 every 3 weeks for 6 cycles.
* The decision to administer radiation therapy will be per the treating physician. If the patient does not receive radiation therapy, then the patient will start MK-3475 every 3 weeks x 4 doses after the completion of chemotherapy. Receives: Drug: MK-3475; Procedure: Surgical resection (standard of care); Drug: Paclitaxel (standard of care); Drug: Carboplatin (standard of care); Radiation: Radiation (standard of care); Procedure: Endometrial biopsy; Procedure: Peripheral blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as Measured by Any Grade Treatment Related Adverse Events Experienced by ≥ 2 Patients
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting
Measured: Through 90 days following last dose of MK-3475 (approximately 56 weeks)
Safety as Measured by Any Grade 3 or Higher Treatment Related Adverse Events
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting
Measured: Through 90 days following last dose of MK-3475 (approximately 56 weeks)
Secondary outcomes (1)
Progression-free Survival (PFS)
- PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measured: Up to 2 years following completion of therapy (median follow-up of 35 months (full range 11.3-46 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study start5 Feb 2016
- Primary completion1 Jan 2019
- Study completion3 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Premal Thaker, M.D., MSc., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630823
- Sponsor's protocol ID
- 201601062
- Status last verified
- Nov 2024
- First submitted
- 10 Dec 2015
- Last updated
- 3 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- 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 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy With MK-3475 in Surgically Resectable Endometrial Carcinoma
- ClinicalTrials.gov ID
- NCT02630823
- Acronym / sponsor ID
- 201601062
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 5 Feb 2016 (actual)
- Primary completion
- 1 Jan 2019 (actual)
- Study completion
- 3 Oct 2020 (actual)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Posted 3 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Due to the high expression of PD-L1 in endometrial cancers as well as in ovarian cancers which are molecularly similar to uterine serous cancers, using pembrolizumab should be beneficial in this patient population. Since the investigators are able to get a pre-treatment research- related endometrial biopsy as well as the surgical specimen post two cycles of pembrolizumab, the investigators will be able to evaluate the mechanism of action of this drug on the endometrial cancer tumor environment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: MK-3475 | Experimental | Drug: MK-3475, Procedure: Surgical resection (standard of care), Drug: Paclitaxel (standard of care), Drug: Carboplatin (standard of care), Radiation: Radiation (standard of care), Procedure: Endometrial biopsy, Procedure: Peripheral blood draw* Patients will undergo endometrial biopsy followed by 2 doses of MK-3475 3 weeks apart. 3-4 weeks after the second dose of MK-3475, the standard of care surgical resection will take place, followed by standard of care adjuvant therapy. Tissue and blood will be collected at the time of surgical resection for immune analysis. For patients whose pathology confirms high-risk features and advanced stage, MK-3475 will be given every 3 weeks starting 4 -6 weeks after completion of adjuvant therapy for a maximum of 4 doses post-surgery. * MK-3475 will be given intravenously at a dose of 200 mg over the course of 30 minutes. * The standard of care chemotherapy will consist of 6 cycles of paclitaxel and carboplatin AUC 5 every 3 weeks for 6 cycles. * The decision to administer radiation therapy will be per the treating physician. If the patient does not receive radiation therapy, then the patient will start MK-3475 every 3 weeks x 4 doses after the completion of chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Diagnosis of FIGO grade 3 endometrioid cancer, serous, clear cell, or mixed high grade endometrial cancer with confirmation on research-related endometrial biopsy.
- Radiographically confirmed endometrial adenocarcinoma of stages III-IV requiring adjuvant therapy. If stage III disease is suspected, there should be multiple pelvic and/or lymph nodes involved.
- Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1.
- Treatment plan must include primary site biopsy followed by resection of the primary tumor site and any metastatic sites at time of surgery.
- At least 18 years of age.
Key exclusion criteria (19 listed)
- FIGO grade 1 or 2 endometrioid cancer.
- Radiographic imaging demonstrating uterine cancer that is probably stage I or II.
- Prior treatment for endometrial cancer.
- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first dose of MK-3475 or has not recovered (i.e., to ≤ grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier.
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 |
|---|---|---|
| MK-3475Also: pembrolizumab, Keytruda | Drug | Arm 1: MK-3475 |
| Surgical resection (standard of care) | Procedure or surgery | Arm 1: MK-3475 |
| Paclitaxel (standard of care)Also: Taxol | Drug | Arm 1: MK-3475 |
| Carboplatin (standard of care)Also: Paraplat, Paraplatin | Drug | Arm 1: MK-3475 |
| Radiation (standard of care) | Radiation | Arm 1: MK-3475 |
| Endometrial biopsy | Procedure or surgery | Arm 1: MK-3475 |
| Peripheral blood draw | Procedure or surgery | Arm 1: MK-3475 |
Primary outcome
Safety as Measured by Any Grade Treatment Related Adverse Events Experienced by ≥ 2 Patients
Time frame: Through 90 days following last dose of MK-3475 (approximately 56 weeks)
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting
Safety as Measured by Any Grade 3 or Higher Treatment Related Adverse Events
Time frame: Through 90 days following last dose of MK-3475 (approximately 56 weeks)
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all adverse event reporting
1 secondary outcome
Progression-free Survival (PFS)
Time frame: Up to 2 years following completion of therapy (median follow-up of 35 months (full range 11.3-46 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Endometrial Cancer
Not yet recruiting
Mind-Body Interventions for the Improvement of Quality of Life, Stress, and Sleep Quality Among Survivors of Breast, Prostate, Endometrial, or Colorectal Cancer
Breast Cancer Stage I, Colorectal Cancer
RecruitingPhase 1/2
Pembrolizumab, Lenvatinib and IL-15 Superagonist N-803 in Combination With HER2 Targeting Autologous Dendritic Cell (AdHER2DC) Vaccine in Participants With Advanced or Metastatic Endometrial Cancer
Endometrial Cancer, Cancer of Endometrium
RecruitingPhase 3
Assessing Survival Outcomes With Checkpoint Inhibition ExteNded vs Discontinued in Endometrial Cancer
Endometrial Adenocarcinoma, Metastatic Endometrial Cancer
RecruitingPhase 2
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer
Metastatic Colorectal Cancer, Metastatic Pancreatic Cancer
RecruitingObservational study
Leveraging Methylated DNA Markers (MDMs) in the Detection of Endometrial Cancer, Ovarian Cancer, and Cervical Cancer
Endometrial Cancer, Cervical Cancer
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.
Premal Thaker, M.D., MSc. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-3475 in people with Endometrial Cancer and Endometrial Carcinoma, run by Washington University School of Medicine 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 17 inclusion and 19 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: finished, as of the sponsor's last update on 3 Jan 2025. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety as Measured by Any Grade Treatment Related Adverse Events Experienced by ≥ 2 Patients (time frame: Through 90 days following last dose of MK-3475 (approximately 56 weeks)). The study lists 2 primary outcomes in all. 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 3 Jan 2025.