Biweekly Actinomycin-D Treatment or Multi-day Methotrexate Protocol in Low-risk Gestational Trophoblastic Neoplasia

• ClinicalTrials.gov Identifier: NCT04562558
• Recruitment Status: Recruiting
• First Posted: September 24, 2020
• Last Update Posted: November 16, 2021
• Sponsor: xiang yang
• Information provided by (Responsible Party): xiang yang, Peking Union Medical College Hospital

Tracking Information

• First Submitted Date: September 13, 2020
• First Posted Date: September 24, 2020
• Last Update Posted Date: November 16, 2021
• Actual Study Start Date: September 29, 2020
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2020)

• Completely remission (CR) rate by single-agent [ Time Frame: from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months ]
  Percentage of participants with complete response by single-agent chemotherapy. A complete response was defined as a normal hCG sustained over 3 weekly measurements.
• Overall completely remission rate [ Time Frame: from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy or multi-agent chemotherapy，assessed up to 12 months ]
  Percentage of participants with complete response by single-agent chemotherapy and those by second line multiple-drug chemotherapy after single-agent failure

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2020)

• The duration needed to achieve complete remission after single-agent chemotherapy [ Time Frame: from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months ]
  The duration needed to achieve complete remission after single-agent in two arms
• The number of courses needed to achieve complete remission after single-agent chemotherapy [ Time Frame: from date of treatment begin until the data serum hCG is normal for 3 consecutive weeks by single-agent chemotherapy，assessed up to 8 months ]
  The number of courses needed to achieve complete remission after single-agent chemotherapy in two arms
• Incidence of Adverse Effects (Grade 3 or Higher) [ Time Frame: through study completion, an average of 3 year ]
  Incidence and severity of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 in two arms
• Effects on menstrual conditions and ovarian function [ Time Frame: Prior to treatment begin，and 6 month after single-agent chemotherapy completion, an average of 2 year ]
  Effects on menstrual conditions and ovarian function measured by Anti-Mullerian hormone（AMH）

• 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: Biweekly Actinomycin-D Treatment or Multi-day Methotrexate Protocol in Low-risk Gestational Trophoblastic Neoplasia
• Official Title: A Prospective，Multicenter，Randomized Trial of Biweekly Single-dose Actinomycin-D Versus Multi-day Methotrexate Protocol for the Treatment of Low-risk Gestational Trophoblastic Neoplasia
• Brief Summary: The investigators conducted a randomized trial to study how well multi-day methotrexate protocol works compared to biweekly single-dose actinomycin D protocol in treating patients with low-risk gestational trophoblastic neoplasia. It is not yet known whether multi-day methotrexate protocol is as effective as biweekly single-dose actinomycin D protocol in treating patients with gestational trophoblastic neoplasia.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A prospective，multicenter，randomized trial with two arms

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Gestational Trophoblastic Tumor
• Gestational Trophoblastic Neoplasia
• Stage I Gestational Trophoblastic Tumor
• Stage II Gestational Trophoblastic Tumor
• Stage III Gestational Trophoblastic Tumor
• Invasive Mole
• Choriocarcinoma

Intervention

• Drug: Methotrexate
  50mg intramuscularly on Days 1, 3, 5, 7 . Repeat every 14 days
  Other Name: MTX
• Drug: Leucovorin
  15mg intramuscularly on Days 2, 4, 6, 8. Repeat every 14 days
  Other Name: Calcium folinate
• Drug: Dactinomycin
  1.25mg/m2 (2mg max dose)intravenous every 14 days.
  Other Name: dactinomycin D

Study Arms

• Experimental: Arm1-Methotrexate
  Patients receive methotrexate intramuscularly（50mg） on Days 1, 3, 5, 7 (4 doses per cycle) with Leucovorin (15mg) on Days 2, 4, 6, 8. Repeat every 14 days. Patients continue on treatment until beta HCG titer is below the institutional normal. Patients then receive 2-3 additional consolidation treatment. If the level of hCG become stationary for at least 2 course of single-agent chemotherapy or rise again, the patient will be referred to multi-course chemotherapy. FAV regimen is preferred, or EMA-CO regimen can also be selected if FAV is unavailable.
  Interventions:

  • Drug: Methotrexate
  • Drug: Leucovorin
• Experimental: Arm 2-Dactinomycin
  Patients will receive IV pulse actinomycin-D (1.25mg/m2，2mg max dos) every 14 days. Patients continue on treatment until beta HCG titer is below the institutional normal. Patients then receive 2-3 additional consolidation treatment.If the level of hCG become stationary for at least 2 course of single-agent chemotherapy or rise again, the patient will be referred to multi-course chemotherapy. FAV regimen is preferred, or EMA-CO regimen can also be selected if FAV is unavailable.
  Intervention: Drug: Dactinomycin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 18, 2020): 176
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically proven low-risk gestational trophoblastic neoplasia (persistent hydatidiform mole or choriocarcinoma), defined as 1 of the following:

  • Less than 10% decrease in the beta human chorionic gonadotropin (HCG) titer over 3 weekly titers
  • Greater than 20% sustained rise in beta HCG titer over two consecutive weeks
  • Histologically proven choriocarcinoma
• Stage I - III disease
• WHO risk score 0-4
• No prior chemotherapy for gestational trophoblastic neoplasia
• Signed informed consent
• Performance status - GOG 0-2
• Laboratory examination： WBC≥3.5×10(9)/L, Granulocyte count≥1.5×10(9)/L, Platelet count≥80×10(9)/L, serum bilirubin≤ 1.5 times the upper limit of normal, transaminase≤ 1.5 times the upper limit of normal, BUN, Creatinine≤ normal。 Fertile patients must use effective contraception during and for one year after study entry

Exclusion Criteria:

• Histologically confirmed placental-site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT)
• primary choriocarcinoma
• WHO risk score >4
• Previous MTX treatment for suspected ectopic pregnancy
• With severe or uncontrolled internal disease, unable to receive chemotherapy;
• Concurrently participating in other clinical trials
• Unable or unwilling to sign informed consents;
• Unable or unwilling to abide by protocol.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Yang Xiang; 86-010-69155635; xiangy@Pumch.cn

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04562558
• Other Study ID Numbers: PUMCH-LRGTN-SINGLE DRUG-0222
• 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
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: xiang yang, Peking Union Medical College Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: xiang yang
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: yang xiang; Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences

• PRS Account: Peking Union Medical College Hospital
• Verification Date: November 2021