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

Primary Purpose

Gestational Trophoblastic Neoplasia

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

PD-1 inhibitor， bevacizumab

About this trial

This is an interventional treatment trial for Gestational Trophoblastic Neoplasia focused on measuring bevacizumab, pd-1, chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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。

Sites / Locations

Women's Hospital School of Medicine Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Double medicine combined

Arm Description

participants received 200mg of PD-1 inhibitors combined 15mg of bevacizumab per square body surface area intravenously every 3 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT04812002

First Posted

March 21, 2021

Last Updated

June 2, 2022

Sponsor

Women's Hospital School Of Medicine Zhejiang University

1. Study Identification

Unique Protocol Identification Number

NCT04812002

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 15, 2021 (Actual)

Primary Completion Date

April 15, 2024 (Anticipated)

Study Completion Date

April 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Women's Hospital School Of Medicine Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gestational Trophoblastic Neoplasia

Keywords

bevacizumab, pd-1, chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Double medicine combined

Arm Type

Experimental

Arm Description

participants received 200mg of PD-1 inhibitors combined 15mg of bevacizumab per square body surface area intravenously every 3 weeks

Intervention Type

Drug

Intervention Name(s)

PD-1 inhibitor， bevacizumab

Other Intervention Name(s)

Camrelizumab for Injection

Intervention Description

Both drugs are given intravenously

Primary Outcome Measure Information:

Title

PFS

Description

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.

Time Frame

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 Measure Information:

Title

ORR

Description

Time Frame

From date of randomization until PD or death from any cause, assessed up to 24 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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。

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Xing Xie, phD

Phone

+8613606705128

panzimin@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Zimin Pan, MD

Phone

+8613758142505

panzimin@zju.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xing Xie, doctor

Organizational Affiliation

Women's Hospital School Of Medicine Zhejiang University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Women's Hospital School of Medicine Zhejiang University

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xing Xie, phD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

17086804

Citation

Lurain JR, Singh DK, Schink JC. Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy. J Reprod Med. 2006 Oct;51(10):767-72.

Results Reference

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PubMed Identifier

23233709

Citation

Alifrangis C, Agarwal R, Short D, Fisher RA, Sebire NJ, Harvey R, Savage PM, Seckl MJ. EMA/CO for high-risk gestational trophoblastic neoplasia: good outcomes with induction low-dose etoposide-cisplatin and genetic analysis. J Clin Oncol. 2013 Jan 10;31(2):280-6. doi: 10.1200/JCO.2012.43.1817. Epub 2012 Dec 10.

Results Reference

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PubMed Identifier

31136884

Citation

Li J, Yue H, Wang X, Chen R, Lu X. Chemotherapy for gestational trophoblastic neoplasia patients with a FIGO score of 12 or greater: A multistudy analysis. Eur J Obstet Gynecol Reprod Biol. 2019 Jul;238:164-169. doi: 10.1016/j.ejogrb.2019.05.023. Epub 2019 May 20.

Results Reference

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PubMed Identifier

30700567

Citation

Anantharaju AA, Pallavi VR, Bafna UD, Rathod PS, R VC, K S, Kundargi R. Role of salvage therapy in chemo resistant or recurrent high-risk gestational trophoblastic neoplasm. Int J Gynecol Cancer. 2019 Mar;29(3):547-553. doi: 10.1136/ijgc-2018-000050. Epub 2019 Jan 29.

Results Reference

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PubMed Identifier

30027717

Citation

Bianconi MI, Otero S, Storino C, Jankilevich G. Role of Capecitabine in the Management of Gestational Trophoblastic Neoplasia: A Drug for Two Settings. J Reprod Med. 2017 May-Jun;62(5-6):250-6.

Results Reference

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PubMed Identifier

18453518

Citation

Wang J, Short D, Sebire NJ, Lindsay I, Newlands ES, Schmid P, Savage PM, Seckl MJ. Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE). Ann Oncol. 2008 Sep;19(9):1578-83. doi: 10.1093/annonc/mdn181. Epub 2008 May 2.

Results Reference

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PubMed Identifier

28060141

Citation

Bolze PA, Patrier S, Massardier J, Hajri T, Abbas F, Schott AM, Allias F, Devouassoux-Shisheboran M, Freyer G, Golfier F, You B. PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes. Int J Gynecol Cancer. 2017 Mar;27(3):554-561. doi: 10.1097/IGC.0000000000000892.

Results Reference

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PubMed Identifier

27362903

Citation

Veras E, Kurman RJ, Wang TL, Shih IM. PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases. Int J Gynecol Pathol. 2017 Mar;36(2):146-153. doi: 10.1097/PGP.0000000000000305.

Results Reference

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

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