eo-adjuvant Pembrolizumab as an alternative treatment for MMRd uterine cancer, a phase II efficacy study
- Conditions
- endometrial cancerUterine cancer10038594
- Registration Number
- NL-OMON53535
- Lead Sponsor
- niversitair Medisch Centrum Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
- Female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed primary diagnosis of G3/CC
MMRd uterine cancer who are intended to be treated with hysterectomy.
- 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 contraceptive guidance 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.
- A WOCBP who has a positive serum pregnancy test at screening.
- 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.
- Has received prior radiotherapy within 2 weeks of start of study treatment or
radition-related toxicities requiring corticosteroids. Note: Two weeks or fewer
of palliative radiotherapy for non-CNS disease with a 1-week washout is
permitted.
- Has received a live vaccine or live-attenuated vaccine within 30 days before
to the first dose of study intervention. Administration of killed vaccines and
Covid vaccines is allowed.
- Has received an investigational agent or has used an investigational device
within 4 weeks prior to study intervention administration.
- 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 except replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid).
- 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 not adequately recovered from major surgery or has ongoing surgical
complications.
- 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 treatin
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the fraction of patients that achieve a major<br /><br>pathologic response (MPR) after 9 cycles of pembrolizumab. MPR was chosen in<br /><br>line with neo-adjuvant vs adjuvant ICB trials in other cancer types (e.g. the<br /><br>NADINA trial; NCT04949113 for melanoma patients) and will be used to inform<br /><br>the design of a randomized follow-up trial. The trial is considered positive if<br /><br>a >=74% MPR rate is observed (see also sample size calculation). </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints are the radiologic response rates, recurrence-free survival<br /><br>(RFS) at 2 years from disease diagnosis, and the safety and tolerability of 9<br /><br>cycles of pembrolizumab. Exploratory endpoints relate to the nature of the<br /><br>immune responses in peripheral blood and tumor, the involvement of Tumor<br /><br>Draining Lymph Nodes (TDLN), and changes in circulating tumor DNA (ctDNA)<br /><br>during treatment.</p><br>