A Single-arm, Multicenter Phase II Study of PD-1 Inhibitor Combined With Neoadjuvant Chemotherapy in Advanced Endometrial Cancer in Clinical Efficacy
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Endometrioid Endometrial Cancer
- Sponsor
- Women's Hospital School Of Medicine Zhejiang University
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Pathologic complete response
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
Exploring the therapeutic effect of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab on advanced stage III-IV endometrial cancer
Detailed Description
Conduct domestic multicenter, prospective phase II single arm clinical trials to answer the following questions： 1. Evaluate the impact of neoadjuvant chemotherapy combined with camrelizumab on the remission rate, surgical complications, and surgical resection rate of advanced stage III-IV endometrial cancer; 2. Evaluate the effect of of neoadjuvant chemotherapy combined with camrelizumab on the survival of patients with advanced III-IV endometrial cancer; 3. Exploring the changes in tumor local immune related factors and cells before and after neoadjuvant chemotherapy and camrelizumab use, as well as the responsiveness of different molecular subtypes of endometrial cancer to neoadjuvant therapy, and screen for biological indicators that predict the effectiveness of camrelizumab.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Endometrial cancer initially diagnosed as stage III non-operable resectable, stage IV (FIGO, 2009 criteria) after imaging evaluation
- •Pathologically confirmed endometrial cancer that looks like endometrial carcinoma
- •Patient age ≥18 years and ≤75 years old
- •ECOG status score of 0-1
- •tolerate surgery and radiotherapy
- •Laboratory tests: WBC ≥3.5×109/L, NEU ≥1.5×109/L, PLT ≥80×109/L, serum ≥80×109/L, serum ≥80×109/L, serum ≥80×109/L, serum ≥80×109/L.
- •×109/L, serum bilirubin ≤1.5 times the high limit of normal value, transaminase ≤1.5 times the high limit of normal value, BUN ≤1.5 times the high limit of normal value.
- •1.5 times of the high limit of normal value, BUN, Cr≤normal value;
- •Able to follow up and good compliance;
- •Able to sign the informed consent form, including compliance with the requirements and restrictions listed in the informed consent form and the program.
Exclusion Criteria
- •Subjects with an active, known, or suspected autoimmune disease, or a history of an autoimmune disease, except for: vitiligo, alopecia areata, Graves' disease, psoriasis, or eczema that has not required systemic therapy within the last 2 years, hypothyroidism that is asymptomatic or requires only stable doses of hormone replacement therapy (due to autoimmune thyroiditis), type 1 diabetes that requires only stable doses of insulin replacement therapy, asthma that subsides completely in childhood and does not require intervention in adulthood, or diseases that do not recur in the absence of external triggers;
- •Prior treatment with immune checkpoint inhibitors, including, but not limited to, other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or any treatment directed against immune co-stimulators (e.g., antibodies directed against ICOS, CD40, CD137, GITR, OX40 targets, etc.) that target any mechanism of immune action against tumors;
- •Known hypersensitivity to any component and/or any excipient of the trial regimen;
- •Immunosuppressive drugs or systemic corticosteroids for immunosuppression (\>10 mg/day of prednisone or other equivalent) within 2 weeks prior to trial dosing; topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids are permitted;
- •Received herbs with antitumor effects or drugs with immunomodulatory effects (e.g., thymidine, interferon, interleukin-2) within 2 weeks prior to the trial;
- •Active systemic infection requiring systemic treatment;
- •Serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia;
- •Patients with untreated chronic hepatitis B, or HBV carriers with chronic hepatitis B virus (HBV) DNA greater than 1,000 IU/mL, or patients with active hepatitis C. Inactive HBsAg carriers, treated hepatitis B patients with stable disease (HBV DNA \< 1000 IU/mL), and cured hepatitis C patients will be eligible for enrollment. HCV antibody-positive subjects will be eligible for the study only if they have a negative HCV RNA test;
- •Known active tuberculosis (TB), patients with suspected active TB should undergo chest X-ray and sputum examination in conjunction with clinical signs and symptoms for exclusion;
- •Immunodeficiency or human immunodeficiency virus (HIV antibody positive);
Arms & Interventions
Neoadjuvant chemotherapy combined with PD-1 inhibitor in FIGO III/IV Endometrial carcinoma
Patients with advanced endometrial cancer were enrolled for 2-3 cycles of neoadjuvant chemotherapy in combination with camrelizumab, with imaging to assess efficacy; intermittent subtractive surgery (transabdominal hysterectomy + bilateral adnexectomies + pelvic lymph node dissection + pelvic and abdominal tumors resections +/- para-abdominal aortic lymph node dissection) was performed in patients with complete remissions (CR)/partial remissions (PR), and continued with 3-4 cycles of neoadjuvant chemotherapy in combination with camrelizumab.
Intervention: Camrelizumab
Neoadjuvant chemotherapy combined with PD-1 inhibitor in FIGO III/IV Endometrial carcinoma
Patients with advanced endometrial cancer were enrolled for 2-3 cycles of neoadjuvant chemotherapy in combination with camrelizumab, with imaging to assess efficacy; intermittent subtractive surgery (transabdominal hysterectomy + bilateral adnexectomies + pelvic lymph node dissection + pelvic and abdominal tumors resections +/- para-abdominal aortic lymph node dissection) was performed in patients with complete remissions (CR)/partial remissions (PR), and continued with 3-4 cycles of neoadjuvant chemotherapy in combination with camrelizumab.
Intervention: Carboplatin
Neoadjuvant chemotherapy combined with PD-1 inhibitor in FIGO III/IV Endometrial carcinoma
Patients with advanced endometrial cancer were enrolled for 2-3 cycles of neoadjuvant chemotherapy in combination with camrelizumab, with imaging to assess efficacy; intermittent subtractive surgery (transabdominal hysterectomy + bilateral adnexectomies + pelvic lymph node dissection + pelvic and abdominal tumors resections +/- para-abdominal aortic lymph node dissection) was performed in patients with complete remissions (CR)/partial remissions (PR), and continued with 3-4 cycles of neoadjuvant chemotherapy in combination with camrelizumab.
Intervention: Paclitaxel
Neoadjuvant chemotherapy combined with PD-1 inhibitor in FIGO III/IV Endometrial carcinoma
Patients with advanced endometrial cancer were enrolled for 2-3 cycles of neoadjuvant chemotherapy in combination with camrelizumab, with imaging to assess efficacy; intermittent subtractive surgery (transabdominal hysterectomy + bilateral adnexectomies + pelvic lymph node dissection + pelvic and abdominal tumors resections +/- para-abdominal aortic lymph node dissection) was performed in patients with complete remissions (CR)/partial remissions (PR), and continued with 3-4 cycles of neoadjuvant chemotherapy in combination with camrelizumab.
Intervention: Surgery
Outcomes
Primary Outcomes
Pathologic complete response
Time Frame: At the end of the patient's treatment, up to 1 years.
Proportion of patients with no tumor cells on postoperative pathology and negative lymph node metastasis
Secondary Outcomes
- Event-free survival (EFS)(Until the end of the 3-year follow-up period, up to 5 years.)
- Surgical complication rate(During and after the surgery, up to 2 years.)
- Remission rate (%) as assessed by RECIST 1.1 criteria(At the end of the patient's treatment, up to 1 years.)
- Overall survival (OS)(Until the end of the 3-year follow-up period, up to 5 years.)
- Adverse Event(during the treatment, up to 5 years.)