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Uterine CancerPhase 1PAMNCT04262089

Neo-adjuvant Pembrolizumab in dMMR/ POLE-EDM Uterine Cancer Patients: a Feasibility Study

A Phase 1 study testing Pembrolizumab (Keytruda) in people with Uterine Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In this feasibility study the investigators intend to treat patients with high mutational uterine cancer with two cycles immune checkpoint inhibition before standard-of-care hysterectomy. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Uterine Cancer
What is being tested?
Pembrolizumab (Keytruda)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteNetherlands
Study dates
1 Nov 2020to 1 Nov 2023
Phase
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

  • Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed primary diagnosis of dMMR/POLE-EDM uterine cancer who are intended to be treated with hysterectomy will be enrolled in this study.
  • Have measurable disease based on RECIST 1.1 on MRI.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, is not a woman of childbearing potential (WOCBP) or agrees to follow the contraceptive guidance in section 5.2 during the treatment period and at least until standard-of-care hysterectomy.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

Who cannot join

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
  • Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
  • Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
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  • 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.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • 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.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • 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 (eg., 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 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.
  • Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

About this study

In this feasibility study the investigators intend to treat patients with high mutational uterine cancer with two cycles immune checkpoint inhibition before standard-of-care hysterectomy.

Read the detailed description

Objective:

The investigators aim to establish proof-of-concept for use of immune checkpoint blockade (ICB) as novel neo-adjuvant therapy in (deficient mismatch repair) dMMR and (Polymerase ε mutation)POLE-EDM uterine cancer (UC). When ICB proves to be feasible as defined in the primary endpoint, a follow-up with a larger multicenter studies to determine clinical efficacy, such as postponing standard-of-care surgery or randomized studies to standard-of-care.

Study design:

The investigators planned a window-of-opportunity study of ICB in primary dMMR UC (n=10) and primary POLE-EDM UC (n=10) patients. ICB (pembrolizumab; anti-PD1) will be administered in two cycles of 3 weeks between diagnosis and standard-of-care hysterectomy.

Tumor responses to pembrolizumab will be assessed 3 weeks after the second cycle of pembrolizumab by a pathologist (primary endpoint) and MRI (secondary endpoint).After treatment with immun checkpoint blockade a hysterectomy will take place (standard-of care). Peripheral blood and tumor samples will be used to evaluate immune responses.

Study population:

Primary dMMR/ POLE-EDM UC patients of any stage and/or grade who are intended to be treated with a hysterectomy recruited from the North-Netherlands oncological region.

Intervention: Pembrolizumab, 200mg IV Q3W for a total of 2 administrations per patient, integrated into standard-of-care protocol prior to surgery. Based on the well-established time lines, the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care.

Main study endpoints:

The primary endpoint is the response rate of the tumor assessed by pathology in uterine cancer patients treated with neo-adjuvant pembrolizumab. The secondary endpoint is the objective response rate of the tumor by MRI using RECIST. Exploratory objectives are immunogenicity, safety and the value of a pipelle biopsy as a predictor for response.

Conditions
Uterine Cancer
Being tested
Pembrolizumab (Keytruda)
Keywords
Uterine cancer, dMMR, POLE-EDM, neo-adjuvant, pembrolizumab
Medical subject headings
Uterine Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab (Keytruda)Drug

    Pembrolizumab (Keytruda), 200mg IV Q3W for a total of 2 administrations per patient, integrated into standard-of-care protocol prior to surgery. Based on the well-established time lines, the interval between diagnosis and standard of care hysterectomy is sufficient to treat patients with two cycles of pembrolizumab without interfering with standard of care.

Study groups in NCT04262089
Study groupRoleWhat they receive
primary dMMR uterine cancer patientsExperimentalprimary dMMR uterine cancer patients
Receives: Drug: Pembrolizumab (Keytruda)
primary POLE-EDM uterine cancer patientsExperimentalprimary POLE-EDM uterine cancer patients
Receives: Drug: Pembrolizumab (Keytruda)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary objective is to characterize pathologic responses (necrosis/viable tumor cells) in uterine cancer patients treated with neo-adjuvant pembrolizumab

    Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for evidence of necrosis and/or viable tumor cells

    Measured: Tumor tissue is collected during standard of care hysterectomy (up to 6-10 weeks after baseline)

  2. The primary objective is to characterize pathologic responses (Degree of immune infiltration) in uterine cancer patients treated with neo-adjuvant pembrolizumab

    Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for degree of immune infiltration.

    Measured: Tumor tissue is collected during standard of care hysterectomy (week 6-10 after baseline)

  3. The primary objective is to characterize pathologic responses (Degrees of inflammation, fibrosis, and mucin) in uterine cancer patients treated with neo-adjuvant pembrolizumab

    Hematoxylin and eosin staining on endometrium tissue collected during standard-of-care hysterectomy will be assessed by an experienced pathologist for degrees of inflammation, fibrosis, and mucin, consistent with an ongoing immune response.

    Measured: Tumor tissue is collected during standard of care hysterectomy (week 6-10 after baseline)

Secondary outcomes (1)

  1. Radiologic response

    To assess the objective response rate of the tumor by MRI using RECIST1.1 in uterine cancer patients treated with 2 cycles neo-adjuvant pembrolizumab

    Measured: MRI is scheduled before start study drug (week 1) and after final study drug ( 6-10 weeks after baseline)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2020
  2. Study start1 Nov 2020
  3. Primary completion17 Apr 2023
  4. Study completion1 Nov 2023

Resources

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
Non-randomised
Intervention model
Parallel groups
Model description
A window-of-opportunity study of ICB in primary dMMR UC (n=10) and primary POLE-EDM UC (n=10) patients.
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04262089
Sponsor's protocol ID
PAM-UMCG-001
Acronym
PAM
Status last verified
Dec 2023
First submitted
28 Jan 2020
Last updated
5 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eerkens AL, Brummel K, Vledder A, Paijens ST, Requesens M, Loiero D, van Rooij N, Plat A, Haan FJ, Klok P, Yigit R, Roelofsen T, de Lange NM, Klomp R, Church D, Ter Elst A, Wardenaar R, Spierings D, Foijer F, Koelzer VH, Bosse T, Bart J, Jalving M, Reyners AKL, de Bruyn M, Nijman HW. Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study. Nat Commun. 2024 Sep 3;15(1):7695. doi: 10.1038/s41467-024-52098-8.

    PubMed 39227583

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab (Keytruda) in people with Uterine Cancer, run by University Medical Center Groningen at 1 site in Netherlands.

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 4 inclusion and 21 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 5 Dec 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 Netherlands. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The primary objective is to characterize pathologic responses (necrosis/viable tumor cells) in uterine cancer patients treated with neo-adjuvant pembrolizumab (time frame: Tumor tissue is collected during standard of care hysterectomy (up to 6-10 weeks after baseline)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04262089, which also lists 1 linked publication.

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 5 Dec 2023.

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