Study of PD-1 Antibody and Bevacizumab in the Treatment of High-risk GTN After Combined Chemotherapy

Study Overview
=================
Brief Summary
-----------------
Gestational trophoblastic Neoplasia（GTN） is a kind of malignant tumor in women of childbearing age. It is easy to metastasized through the blood system in the early stage, so it is a relatively malignant tumor. The tumor is highly sensitive to chemotherapy, and low-risk patients have good prognosis, with survival rate and cure rate approaching 100%, but high-risk patients are prone to drug resistance, or relapse after remission. For relapsed, refractory, high-risk GTN, multiple remedies have been reported in the literature, but the remission rate is only 75-80%. For relapsed or refractory high-risk GTN, multiple remedies have been reported in the literature, but the remission rate is only 75-80%. Currently, targeted therapy and immunotherapy are widely used in various refractory solid tumors. For GTN, there are also a number of related studies. In this study, PD-1 inhibitors combined with bevacizumab were used to treat refractory high-risk GTN with relapse or drug resistance after receiving previous second-line or above multidrug combination therapy, to study the efficacy and safety of the treatment regimen.

Detailed Description
-----------------
In this study, PD-1 inhibitors combined with bevacizumab were used to treat refractory high-risk trophoblastic tumor (GTN) with relapse or drug resistance after receiving previous two-line or above multidrug combination therapy, and the efficacy and safety of the two drugs were evaluated. Patients who meet the requirements will sign the informed consent and be enrolled voluntarily. This project is a single-arm study without a control group. Twenty patients are expected to be enrolled, and there are 4 centers competing for enrollment. All patients received at least two-line multidrug combination therapy, and some patients may have undergone or planned surgery and/or radiation therapy. Through the HCG value and measurable changes in the size of the lesions, we can understand the changes of the disease. The primary endpoints were PFS and ORR Whenever, for whatever reason, the subject does not complete the clinical trial observation, is considered to be an abscission case. When the subject falls off, the researcher must fill in the reason for the fall off in the CRF, and contact the subject as much as possible, complete the items that can be evaluated, and record the time of the last medication to prepare for the analysis of its efficacy and safety. The CRF should be kept for future reference

Official Title
-----------------
Phase II Single-arm Clinical Study of PD-1 Antibody and Bevacizumab in the Treatment of Relapsed or Refractory High-risk Gestational Trophoblasitc Neoplasia After Second-line or Above Combined Chemotherapy

Conditions
-----------------
Gestational Trophoblastic Neoplasia

Intervention / Treatment
-----------------
* Drug: PD-1 inhibitor， bevacizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Informed Consent Clinically diagnosed as recurrent or drug-resistant trophoblastic tumor After treatment with at least two or more multidrug chemotherapy regimens Survival is expected to exceed 3 months Age ≥18 years, age ≤75 years Karnofsky score ≥60分，ECOG score ≤2分 No serious complications Take effective contraceptives during treatment Patients can be followed up as required Blood test within 3 days: ANC≥1.5×109/L, PT ≥100×109/L, Hb≥90g/L, BIL ≤ 1.5 times of the high limit of normal value, ALT/ALST ≤ 1.5 times of the high limit of normal value, BUN and Cr≤ normal value Coagulation function, thyroid function and myocardial enzyme in the normal range Exclusion Criteria: Previously, he had received anti-PD-1, anti-PD-L1, bevacizumab and other drugs; Within 2 weeks before the first administration, he had received anticancer Chinese patent medicine or immunomodulatory drugs; Within 2 years before the first administration, he had received active autoimmune disease requiring systemic treatment; Were receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to first administration; Clinically uncontrollable pleural effusion/peritoneal effusion is present; Allergic to PD-1 monoantibody, bevacizumab and other active ingredients or excipients； Failure to fully recover from toxicity and/or complications； History of HIV infection, untreated active hepatitis B, and active HCV infection subjects； Live vaccine was administered within 30 days prior to the first dose； Patients with serious or uncontrollable medical conditions who are not suitable for chemotherapy； Participating in clinical trials of other drugs at the same time or 4 weeks before the first administration。

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double medicine combined<br>participants received 200mg of PD-1 inhibitors combined 15mg of bevacizumab per square body surface area intravenously every 3 weeks | Drug: PD-1 inhibitor， bevacizumab<br>* Both drugs are given intravenously<br>* Other names: Camrelizumab for Injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. | From date of randomization until the date of first documented progression or death from any cause, whichever occurred first, or last follow-up for patients alive without progression, assessed up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR is defined as the rate of CR or PR.Partial response (PR) is defined as a reduction of HCG by 50% or more from the starting value in continuous measurements; Complete response (CR) is defined as HCG normalization of continuous measurements at least two weeks intervals. | From date of randomization until PD or death from any cause, assessed up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bevacizumab, pd-1, chemotherapy