PD-1 Inhibitor Combined With Progesterone Treatment in FST for Patients With MMRd Endometrial Cancer

Not Applicable

Not yet recruiting

Conditions: Mismatch Repair Deficiency
Endometrioid Carcinoma
Endometrial Cancer

Interventions: Drug: Sintilimab or Pembrolizumab and medroxyprogesterone acetate (MPA)/ megestrol acetate (MA)

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
PD-1 Inhibitor Combined With Progesterone Treatment	Sintilimab or Pembrolizumab and medroxyprogesterone acetate (MPA)/ megestrol acetate (MA)	All participants

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Pregnancy rate	1 year after CR	A pregnancy test shows pregnancy after CR.
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.
Live birth rate	1 year after pregnancy	The live birth rate is defined as the ratio of live births to pregnancies.
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.

Locations (1): Peking University People's Hospital
🇨🇳
Beijing, Beijing, China