Endometrial Cancer, Endometrioid Carcinoma, Mismatch Repair Deficiency
Conditions
Keywords
Fertility preservation, Endometrioid Carcinoma, PD-1 inhibitor
Brief summary
The objective of this study was to investigate the feasibility of a PD-1 inhibitor in combination with progesterone as a means of preserving fertility in patients with early-stage mismatch repair-deficient (MMRd) endometrial cancer who wish to preserve fertility.
Detailed description
Endometrial cancer (EC) is a prevalent gynecological cancer with an escalating global incidence. The standard treatment for endometrial cancer is total hysterectomy and bilateral salpingo-oophorectomy. However, given the rising incidence of endometrial cancer in younger individuals and the the delay in the age of human reproduction, the conservation of endometrial cancer has garnered heightened attention. Clinical practice has demonstrated that high-dose progesterone can reverse the lesioned endometrium, thereby providing a rationale for the conservative treatment of early-stage endometrial cancer. PD-1 inhibitor has been utilized as a salvage treatment in many cancers including ovarian cancer, cervical cancer, lung cancer, gastric cancer and endometrial cancer. As endometrial cancer showed MMRd rates, it is assumed to be highly responsive to PD-1 inhibitor treatment. Previous literature has reported that the efficacy of progesterone therapy is limited in patients with a MMRd status.Here we want to investigate the feasibility of PD-1 inhibitor combined with progesterone in early stage endometrial cancer patients who want to preserve fertility.
Interventions
DRUGSintilimab or Pembrolizumab and medroxyprogesterone acetate (MPA)/ megestrol acetate (MA)
1. Sintilimab or Pembrolizumab 200mg intravenous injection, every 3 weeks 2. MA, 320mg/MPA, 500mg, po, once a day
Sponsors
Peking University People's Hospital
Peking Union Medical College Hospital
Peking University Third Hospital
Huazhong University of Science and Technology
Tianjin Medical University
Shandong University
Shengjing Hospital
Beijing Chao Yang Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Be between the ages of 18-45 years old; * Stage IA (FIGO 2009) ; * Confirmed diagnosis of endometrial adenocarcinoma G1-G2 based upon D\&C or hysteroscopy; * Molecular classification of MMRd, determined by immunohistochemical (IHC) for MMR proteins and by the second generation sequencing (NGS) or microsatellite polymerase chain reaction (PCR); * With a strong desire for fertility preservation; * Sign the informed consent.
Exclusion criteria
* Stage IB(FIGO 2009) and above； * Tumour differentiation of G3 or non-endometrioid adenocarcinoma； * Complicated with any other malignancy； * Contraindicated to conservative treatment or the use of pharmaceuticals. * Contraindications to pregnancy, or judged by the researcher to be unfit for pregnancy or delivery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission (CR) rate | From start of treatment to trial completion, an average of 3 months | No endometrioid carcinoma or any proliferative lesion is found by pathology; imaging examination shows no evidence of a tumor |
| Time to CR | From start of treatment to trial completion, an average of 3 months | Time to CR was calculated from the commencement of fertility-preserving treatment to the date of the initial hysteroscopic examination to confirm CR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence rate | 6 months, 1 year, 2 year, 3 year, 4 year, 5 year after CR | After complete remission, there is evidence of recurrence in pathology, and the imaging examination shows that the lesion recurrences. |
| Pregnancy rate | 1 year after CR | A pregnancy test shows pregnancy after CR. |
| Live birth rate | 1 year after pregnancy | The live birth rate is defined as the ratio of live births to pregnancies. |
| Pathological biomarker | From the start of treatment to CR，including 3 months, 6 months, 9 months, and so forth. | pathological markers(such as Ki-67, estrogen receptor, progesterone receptor, p53, PTEN, MLH1, PMS2, MSH2, and MSH6) at each hysteroscopy |
| CA125 | From the start of treatment to trial completion，including 3 months, 6 months, 9 months, and so forth. | Used as a tumor marker for disease monitoring |
| Adverse reactions | From the start of treatment to trial completion，including 3 months, 6 months, 9 months, and so forth. | Any unfavorable response resulting from the administration of any pharmaceutical agent utilized as part of the therapeutic regimen. |
Countries
China
Contacts
CONTACTJianliu Wang, Professor
CONTACTYiqin Wang
STUDY_CHAIRJianliu Wang, Professor
Peking University People's Hospital
Outcome results
None listed