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

NCT ID: NCT04812002

Last Updated: 2022-06-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2026-04-15

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

Conditions

Gestational Trophoblastic Neoplasia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Double medicine combined

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

Group Type: EXPERIMENTAL

PD-1 inhibitor， bevacizumab

Intervention Type: DRUG

Both drugs are given intravenously

Interventions

PD-1 inhibitor， bevacizumab

Both drugs are given intravenously

Intervention Type: DRUG

Other Intervention Names

Camrelizumab for Injection

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent

2. Clinically diagnosed as recurrent or drug-resistant trophoblastic tumor

3. After treatment with at least two or more multidrug chemotherapy regimens

4. Survival is expected to exceed 3 months

5. Age ≥18 years, age ≤75 years

6. Karnofsky score ≥60分，ECOG score ≤2分

7. No serious complications

8. Take effective contraceptives during treatment

9. Patients can be followed up as required

10. 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

11. Coagulation function, thyroid function and myocardial enzyme in the normal range

Exclusion Criteria

1. Previously, he had received anti-PD-1, anti-PD-L1, bevacizumab and other drugs;

2. Within 2 weeks before the first administration, he had received anticancer Chinese patent medicine or immunomodulatory drugs;

3. Within 2 years before the first administration, he had received active autoimmune disease requiring systemic treatment;

4. Were receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to first administration;

5. Clinically uncontrollable pleural effusion/peritoneal effusion is present;

6. Allergic to PD-1 monoantibody, bevacizumab and other active ingredients or excipients；

7. Failure to fully recover from toxicity and/or complications；

8. History of HIV infection, untreated active hepatitis B, and active HCV infection subjects；

9. Live vaccine was administered within 30 days prior to the first dose；

10. Patients with serious or uncontrollable medical conditions who are not suitable for chemotherapy；

11. Participating in clinical trials of other drugs at the same time or 4 weeks before the first administration。

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Women's Hospital School Of Medicine Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xing Xie, doctor

Role: PRINCIPAL_INVESTIGATOR

Women's Hospital School Of Medicine Zhejiang University

Locations

Women's Hospital School of Medicine Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xing Xie, phD

Role: CONTACT

panzimin@163.com

+8613606705128

Zimin Pan, MD

Role: CONTACT

panzimin@zju.edu.cn

+8613758142505

Facility Contacts

Xing Xie, phD

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 17086804 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23233709 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31136884 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30700567 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30027717 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18453518 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28060141 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27362903 (View on PubMed)

Other Identifiers

CSEM018

Identifier Type: -

Identifier Source: org_study_id