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Camrelizumab Plus Apatinib in Patients With High-risk Gestational Trophoblastic Neoplasia

Primary Purpose

Gestational Trophoblastic Neoplasia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Camrelizumab plus apatinib CohortA
Camrelizumab plus apatinib Cohort B
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gestational Trophoblastic Neoplasia

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort A

Cohort B

Arm Description

Population: ultra high-risk gestational trophoblastic neoplasia

Population: high-risk chemo-refractory or relapsed gestational trophoblastic neoplasia

Outcomes

Primary Outcome Measures

Cohort A: Complete remission rate
The proportion of patients achieving complete remission. Complete remission is defined as normal serum β-hCG level measured for 3 consecutive weeks.
Cohort B: Objective response rate
The proportion of patients with complete or partial response according to serum β-hCG level. Partial response is defined as a ≥50% decrease in β-hCG level from baseline after 2 cycles.

Secondary Outcome Measures

Cohort A: Objective response rate
The proportion of patients with complete or partial response according to serum β-hCG level.
Cohort A: Progression-free survival
The time from the treatment initiation to disease progression or death, whichever comes first. Disease progression is defined as any increase in serum β-hCG level from baseline after 2 cycles of treatment or the presence of new metastatic lesions.
Cohort A: Overall survival
The time from the treatment initiation to the date of death or last follow-up.
Cohort A: Duration of response
The time from the first evidence of response to disease progression or death, whichever comes first.
Cohort A: Frequency and severity of adverse events
Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) which is used to evaluate the grade of adverse events, to observe any adverse event and serious adverse event that occurred in all patients during the clinical study period, including abnormal laboratory examination results, clinical manifestations and vital signs, to record their clinical manifestation characteristics, severity, occurrence time, duration, corresponding treatment and prognosis, and to determine their relationship with the study drug.
Cohort B: Progression-free survival
The time from the treatment initiation to disease progression or death, whichever comes first.
Cohort B: Duration of response
The time from the first evidence of response to disease progression or death, whichever comes first.
Cohort B: Overall survival
The time from the treatment initiation to the date of death or last follow-up.
Cohort B: Frequency and severity of adverse events
Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) .

Full Information

First Posted
November 6, 2021
Last Updated
July 7, 2022
Sponsor
Peking Union Medical College Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05139095
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2022 (Actual)
Primary Completion Date
December 1, 2023 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
73 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A
Arm Type
Experimental
Arm Description
Population: ultra high-risk gestational trophoblastic neoplasia
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
Population: high-risk chemo-refractory or relapsed gestational trophoblastic neoplasia
Intervention Type
Drug
Intervention Name(s)
Camrelizumab plus apatinib CohortA
Other Intervention Name(s)
Camrelizumab plus apatinib and multi-drug chemotherapy
Intervention Description
Cohort A: Camrelizumab (200 mg q2w iv) concomitantly with apatinib (250 mg qd po) and EMA/CO [etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine] every 2 weeks. For certain patients with high tumor burden, 1-2 cycles of low-dose chemotherapy (actinomycin D 500 ug and etoposide 100mg/m2, D1-3) will be administered, then followed by EMA/CO. The observation period is 14 days.
Intervention Type
Drug
Intervention Name(s)
Camrelizumab plus apatinib Cohort B
Other Intervention Name(s)
Camrelizumab plus apatinib and multi-drug chemotherapy
Intervention Description
Cohort B: Camrelizumab (200 mg q3w iv) concomitantly with apatinib (250 mg qd po) and multi-drug chemotherapy. The multi-drug chemotherapy regimen will be chosen by the investigator (chemotherapy regimen: EMA/CO [etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine]; or EMA/EP [etoposide, methotrexate and actinomycin-D/etoposide, cisplatin]; or FAEV [floxuridine, actinomycin-D, etoposide, vincristine]). The observation period is 21 days.
Primary Outcome Measure Information:
Title
Cohort A: Complete remission rate
Description
The proportion of patients achieving complete remission. Complete remission is defined as normal serum β-hCG level measured for 3 consecutive weeks.
Time Frame
up to one year
Title
Cohort B: Objective response rate
Description
The proportion of patients with complete or partial response according to serum β-hCG level. Partial response is defined as a ≥50% decrease in β-hCG level from baseline after 2 cycles.
Time Frame
up to one year
Secondary Outcome Measure Information:
Title
Cohort A: Objective response rate
Description
The proportion of patients with complete or partial response according to serum β-hCG level.
Time Frame
up to one year
Title
Cohort A: Progression-free survival
Description
The time from the treatment initiation to disease progression or death, whichever comes first. Disease progression is defined as any increase in serum β-hCG level from baseline after 2 cycles of treatment or the presence of new metastatic lesions.
Time Frame
up to one year
Title
Cohort A: Overall survival
Description
The time from the treatment initiation to the date of death or last follow-up.
Time Frame
up to one year
Title
Cohort A: Duration of response
Description
The time from the first evidence of response to disease progression or death, whichever comes first.
Time Frame
up to one year
Title
Cohort A: Frequency and severity of adverse events
Description
Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) which is used to evaluate the grade of adverse events, to observe any adverse event and serious adverse event that occurred in all patients during the clinical study period, including abnormal laboratory examination results, clinical manifestations and vital signs, to record their clinical manifestation characteristics, severity, occurrence time, duration, corresponding treatment and prognosis, and to determine their relationship with the study drug.
Time Frame
up to one year
Title
Cohort B: Progression-free survival
Description
The time from the treatment initiation to disease progression or death, whichever comes first.
Time Frame
up to one year
Title
Cohort B: Duration of response
Description
The time from the first evidence of response to disease progression or death, whichever comes first.
Time Frame
up to one year
Title
Cohort B: Overall survival
Description
The time from the treatment initiation to the date of death or last follow-up.
Time Frame
up to one year
Title
Cohort B: Frequency and severity of adverse events
Description
Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) .
Time Frame
up to one year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Woman aged 18-60 years; Previously untreated patients with ultra high-risk GTN(Cohort A) or high-risk chemo-refractory or relapsed GTN (Cohort B); 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); 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); Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Patients with abnormal serum hCG level (≥5 IU/L); Expected survival ≥ 4 months; 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). 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. 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: 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; Other malignancies in the past 3 years; Immunosuppressive drugs used within 14 days prior to the first dose of camrelizumab; any active autoimmune disease or a history of autoimmune disease; Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite with the optimal drug therapy); 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; 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; 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; With a history of psychotropic drug abuse and are unable to withdraw the psychotropic drug, or have mental disorders; Major surgery performed within 4 weeks before the first dose of study drug, or open wounds or fractures; 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; Routine urine test indicating urinary protein ++ or more, or confirmed urinary protein ≥1·0 g within 24 hours; 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; Other reasons as judged by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yang Xiang
Phone
010-69156068
Email
XiangY@pumch.cn
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
xiang yang

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Camrelizumab Plus Apatinib in Patients With High-risk Gestational Trophoblastic Neoplasia

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