Toripalimab Plus Actinomycin-D as Fist-Line Treatment for GTN With FIGO Score 7 (TA7)

• ClinicalTrials.gov Identifier: NCT06020755
• Recruitment Status: Not yet recruiting
• First Posted: September 1, 2023
• Last Update Posted: September 5, 2023
• Sponsor: Peking Union Medical College Hospital
• Collaborators: Obstetrics & Gynecology Hospital of Fudan University; Shengjing Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Henan Cancer Hospital; Gansu Provincial Maternal and Child Health Care Hospital; Dalian Maternity and Child Care Hospital; The First Affiliated Hospital of Xiamen University; Sichuan Cancer Hospital & Institute; Shanghai Junshi Bioscience Co., Ltd.
• Information provided by (Responsible Party): xiang yang, Peking Union Medical College Hospital

Tracking Information

• First Submitted Date: August 25, 2023
• First Posted Date: September 1, 2023
• Last Update Posted Date: September 5, 2023
• Estimated Study Start Date: September 2023
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2023)

Complete remission rate [ Time Frame: up to one year ]

The proportion of patients achieving complete remission. Complete remission is defined as normal serum β-hCG level measured for 4 consecutive weeks.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 31, 2023)

• Objective response rate [ Time Frame: up to one year ]
  The proportion of patients with complete or partial response according to serum β-hCG level.
• Progression-free survival [ Time Frame: up to one year ]
  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.
• Disease control rate [ Time Frame: up to one year ]
  The proportion of patients with complete response, partial response, or stable disease according to serum β-hCG level.
• Duration of response [ Time Frame: up to one year ]
  The time from the first evidence of response to disease progression or death, whichever comes first.
• Overall survival [ Time Frame: up to one year ]
  The time from the treatment initiation to the date of death or last follow-up.
• Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: up to one year ]
  Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) .
• Ovarian function [ Time Frame: up to one year ]
  Determine ovarian function as assessed by anti-Müllerian hormone (AMH)
• Quality of life of cancer patients [ Time Frame: up to one year ]
  Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30)
• Cancer specific rehabilitation [ Time Frame: up to one year ]
  Assessed by Cancer rehabilitation evaluation system-short form (CARES-SF)
• Reproductive concerns after cancer [ Time Frame: up to one year ]
  Assessed by Reproductive Concerns After Cancer (RCAC) scale

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Toripalimab Plus Actinomycin-D as Fist-Line Treatment for GTN With FIGO Score 7
• Official Title: Efficacy and Safety of Toripalimab Plus Actinomycin-D as Fist-Line Treatment in Patients With Gestational Trophoblastic Neoplasia With FIGO Score 7: A Single-Arm, Multicenter, Phase II Trial

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of toripalimab plus actinomycin-D as fist-line treatment in patients with gestational trophoblastic neoplasia with FIGO score 7. The main questions it aims to answer are:

• Whether toripalimab plus actinomycin-D as fist-line treatment can achieve a high complete response rate.
• Whether an equally high cure rate can be achieved by multi-drug chemotherapy as second-line treatment in patients who have failed fist-line treatment with toripalimab plus actinomycin-D.

Participants will receive toripalimab plus actinomycin-D. Treatment will be continued until disease progression, unacceptable toxicity, or withdrawal of consent. Treatment will be completed after 4 consolidation cycles.

Detailed Description

The goal of this clinical trial is to evaluate the efficacy and safety of toripalimab plus actinomycin-D as fist-line treatment in patients with gestational trophoblastic neoplasia with FIGO score 7.

Eligible Participants will receive toripalimab (200mg q2w intravenous) plus actinomycin-D (1.25mg/m2，2mg max dose, intravenous). After normalization of serum β-human chorionic gonadotropin (β-hCG) levels, patients will receive 4 cycles of consolidation 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), disease control rate, duration of response, 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) safety, biomarker, ovarian function and quality of life.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gestational Trophoblastic Neoplasia

Intervention

• Drug: Toripalimab
  200mg q2w intravenous
• Drug: Actinomycin-D
  1.25mg/m2，2mg max dose, q2w, intravenous

Study Arms

Experimental: Toripalimab Plus Actinomycin-D

Toripalimab 200mg intravenously(IV) every 2 weeks (Q2W) Actinomycin-D 1.25mg/m2，2mg max dos, intravenously(IV) every 2 weeks (Q2W)

Interventions:

• Drug: Toripalimab
• Drug: Actinomycin-D

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 31, 2023): 17
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Diagnosed as GTN:

   There is a histologic diagnosis of choriocarcinoma or invasive mole. Postmolar GTN: The plateau of β-hCG (±10%) lasts for four measurements over a period of 3 weeks or longer (days 1, 7, 14, 21). There is a rise (>10%) in β-hCG for three consecutive weekly measurements over at least a period of 2 weeks or more (days 1, 7, 14).

   GTN after nonmolar pregnancy: There is a rise after decease, or a plateau of β-hCG 4 weeks after abortion, ectopic pregnancy, or term delivery. Pregnancy residue or new pregnancy have been ruled out.

2. Patients with a FIGO score of 7.
3. Signed informed consent.
4. No previous immunotherapy, chemotherapy, or radiotherapy.
5. Woman aged 18-60 years.
6. Expected survival ≥ 6 months.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 7 days before first dose.
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 ≤1.5×ULN, alanine aminotransferase and aspartate aminotransferase ≤2·5×ULN, INR, PT or APTT ≤1.5×ULN, thyroid stimulating hormone ≤ULN (if thyroid stimulating hormone is abnormal, normal T3 and T4 can also be acceptable).

Exclusion Criteria:

1. Histologically confirmed placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT).
2. Histologically confirmed primary choriocarcinoma.
3. Other malignancies in the past 3 years.
4. Prior systemic anti-cancer treatment, including chemotherapy and radiotherapy.
5. Live vaccines injected within 30 days before the first dose of study drug;
6. Systemic immune stimulant agent (such as a bacterial or viral vaccine, colony-stimulating factors, interferon, interleukin, and combined vaccine) was used 6 weeks before administration or within the 5 half-lives of the drug, whichever is shorter.
7. Previous treatment with immunotherapy drugs (including antibodies targeting PD-1, PD-L1, PD-L2, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimeric antigen receptor T-cell therapy, and other immunotherapy).
8. Known hypersensitivity or allergy to actinomycin-D, toripalimab or any of their excipients.
9. Any active autoimmune disease requiring systemic treatment during the past 2 years.
10. History or current status of non-infectious pneumonia requiring steroid treatment.
11. Receiving steroid hormones (prednisone dose > 10mg/ day) or other immunosuppressants within 14 days before enrollment, excluding those on hormone replacement therapy.
12. Active infection that requires systemic treatment.
13. Human immunodeficiency virus infection or known acquired immunodeficiency syndrome, active hepatitis B, hepatitis C.
14. History of psychotropic drug abuse and are unable to withdraw the psychotropic drug, or have mental disorders.
15. 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.
16. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite with the optimal drug therapy).
17. Abnormal coagulation (international normalized 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.
18. History of cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 3 months before enrolment.
19. 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.
20. A history of allogeneic stem cell transplantation or organ transplantation.
21. Other reasons as judged by the investigator.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Yang Xiang; +861069156068; xiangy@pumch.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT06020755
• Other Study ID Numbers: TA7-GTN-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: xiang yang, Peking Union Medical College Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Peking Union Medical College Hospital
• Original Study Sponsor: Same as current

Collaborators

• Obstetrics & Gynecology Hospital of Fudan University
• Shengjing Hospital
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Henan Cancer Hospital
• Gansu Provincial Maternal and Child Health Care Hospital
• Dalian Maternity and Child Care Hospital
• The First Affiliated Hospital of Xiamen University
• Sichuan Cancer Hospital & Institute
• Shanghai Junshi Bioscience Co., Ltd.

• Investigators: Not Provided
• PRS Account: Peking Union Medical College Hospital
• Verification Date: September 2023