Brief Title
Camrelizumab Plus Apatinib in Patients With High-risk Gestational Trophoblastic Neoplasia
Official Title
Camrelizumab Plus Apatinib in Patients With High-risk Gestational Trophoblastic Neoplasia: a Cohort, Open-label, Phase 2 Trial
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of camrelizumab and apatinib
as combination therapy in patients with ultra high-risk (Cohort A) and high-risk
chemo-refractory or relapsed (Cohort B) gestational trophoblastic neoplasia (GTN). Eligible
patients will receive camrelizumab plus apatinib plus chemotherapy. Treatment will be
continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Detailed Description
The purpose of this study is to evaluate the efficacy and safety of camrelizumab and apatinib
as combination therapy in patients with ultra high-risk (Cohort A) and high-risk
chemo-refractory or relapsed (Cohort B) gestational trophoblastic neoplasia (GTN).
Cohort A: Eligible patients will receive camrelizumab (200mg q2w iv) plus apatinib (250 mg qd
po) plus chemotherapy. After normalization of serum β-human chorionic gonadotropin (β-hCG)
levels, patients will receive 4 cycles of consolidation chemotherapy combined with
camrelizumab plus apatinib and then 6 months of camrelizumab plus apatinib as maintenance
treatment. Treatment will be continued until completion of treatment, disease progression,
unacceptable toxicity, or withdrawal of consent.The primary endpoint is complete remission
rate (the proportion of patients achieving complete remission). Secondary endpoints include
objective response rate (the proportion of patients achieving complete remission and partial
remission), progression-free survival (time from the treatment initiation to disease
progression or death, whichever comes first), overall survival (time from the treatment
initiation to the date of death or last follow-up), duration of response (time from the first
evidence of response to disease progression or death, whichever comes first) and safety.
Cohort B: Eligible patients will receive camrelizumab (200mg q3w iv) plus apatinib (250 mg qd
po) plus chemotherapy. Treatment will be continued until disease progression, unacceptable
toxicity, or withdrawal of consent. Patients will receive 6 cycles of consolidation therapy
if achieving a complete response. The primary endpoint is objective response rate. Secondary
endpoints include progression-free survival, duration of response, overall survival and
safety.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Cohort A: Complete remission rate
Secondary Outcome
Cohort A: Objective response rate
Condition
Gestational Trophoblastic Neoplasia
Intervention
Camrelizumab plus apatinib CohortA
Study Arms / Comparison Groups
Cohort A
Description: Population: ultra high-risk gestational trophoblastic neoplasia
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
73
Start Date
January 27, 2022
Completion Date
June 1, 2024
Primary Completion Date
December 1, 2023
Eligibility Criteria
Inclusion Criteria:
1. Woman aged 18-60 years;
2. Previously untreated patients with ultra high-risk GTN（Cohort A） or high-risk
chemo-refractory or relapsed GTN (Cohort B);
3. No previous chemotherapy or radiotherapy for ultra high-risk GTN（Cohort A）and have
previously received two or more lines of combination chemotherapies for high-risk
chemo-refractory or relapsed GTN (Cohort B);
4. Patients with ultra high-risk GTN (FIGO stages I-III: score ≥13 and stage IV)
according to the International Federation of Gynecology and Obstetrics (FIGO) 2000
staging and risk factor scoring system（Cohort A）and patients with a prognostic score
≥7 (Cohort B);
5. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
6. Patients with abnormal serum hCG level (≥5 IU/L);
7. Expected survival ≥ 4 months;
8. The function of vital organs meets the following requirements:
hemoglobin ≥90 g/L, absolute neutrophil count ≥1·5×109/L, platelets ≥100×109/L;
creatinine ≤1·5 × upper limit of normal (ULN), urea nitrogen ≤2·5×ULN; total bilirubin
≤ULN, alanine aminotransferase and aspartate aminotransferase ≤2·5×ULN, albumin ≥25
g/L; thyroid stimulating hormone ≤ULN (if thyroid stimulating hormone is abnormal,
normal T3 and T4 can also be acceptable).
9. Female patients of childbearing age must exclude pregnancy and are willing to use a
medically approved high-efficiency contraceptive (e.g., intrauterine device,
contraceptive or condom) during the study period and within 6 months of the last study
drug administration.
10. The patient should be aware of the purpose of the study and the operations required by
the study and volunteer to participate in the study before sign the informed consent
form.
Exclusion Criteria:
1. Previous treatment with immunotherapy drugs (including antibodies targeting PD-1,
PD-L1, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimeric antigen
receptor T-cell therapy, and other immunotherapy), anti-angiogenic small-molecule
tyrosine kinase inhibitors (such as pazopanib, sorafenib, or regorafenib), or
anti-angiogenic monoclonal antibodies (such as bevacizumab); live vaccines injected
within 4 weeks before the first dose of study drug; other clinical trials of
antitumour drugs within 4 weeks before the first dose of study drug;
2. Other malignancies in the past 3 years;
3. Immunosuppressive drugs used within 14 days prior to the first dose of camrelizumab;
any active autoimmune disease or a history of autoimmune disease;
4. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood
pressure ≥90 mmHg, despite with the optimal drug therapy);
5. Grade II or higher myocardial ischemia, myocardial infarction or poorly controlled
arrhythmia (females with QTc interval ≥470 ms); grade III to IV cardiac insufficiency
according to New York Heart Association (NYHA) criteria, or cardiac color Doppler
ultrasound evidence of left ventricular ejection fraction <50%; myocardial infarction,
NYHA grade II or above heart failure, uncontrolled angina, uncontrolled severe
ventricular arrhythmia, clinically significant pericardial disease, or
electrocardiogram suggesting acute ischemia or abnormal active conduction system
occurring within 6 months before enrolment;
6. Abnormal coagulation (international normalised ratio >1·5×ULN or prothrombin time
>ULN+4 seconds or activated partial thromboplastin time >1·5×ULN), with bleeding
tendency or undergoing thrombolysis or anticoagulant therapy;
7. Severe infections within 4 weeks prior to the first dose of study drug (e.g., need of
intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained
fever (>38·5°C) during screening or the first dose of study drug;
8. With a history of psychotropic drug abuse and are unable to withdraw the psychotropic
drug, or have mental disorders;
9. Major surgery performed within 4 weeks before the first dose of study drug, or open
wounds or fractures;
10. Obvious factors affecting oral drug absorption, such as inability to swallow, chronic
diarrhea and intestinal obstruction, or sinus or perforation of empty organs within 6
months;
11. Routine urine test indicating urinary protein ++ or more, or confirmed urinary protein
≥1·0 g within 24 hours;
12. Human immunodeficiency virus infection or known acquired immunodeficiency syndrome,
active hepatitis B (HBV DNA >500 IU/mL), hepatitis C (hepatitis C antibody positive,
and HCV-RNA higher than the lower limit of the analysis method) or co-infection with
hepatitis B and hepatitis C;
13. Other reasons as judged by the investigator.
Gender
Female
Ages
18 Years - 60 Years
Accepts Healthy Volunteers
No
Contacts
, 010-69156068, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT05139095
Organization ID
MA-GTN-II-001
Responsible Party
Sponsor
Study Sponsor
Peking Union Medical College Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor
, ,
Verification Date
November 2021