Clinical trial NCT05411705: Efficacy and Safety of rhTPO's Prophylactic Treatment of CTIT in Patients With High Risk of Cardiac Injury
Official title: A Multicenter Randomized Controlled Study to Assess the Efficacy and Safety of rhTPO's Prophylactic Treatment of Cancer Treatment-induced Thrombocytopenia in Patients With High Risk of Treatment-induced Cardiac Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cancer Treatment Induced Thrombocytopenia
Keywords: rhTPO
Prophylactic Treatment
Cancer Treatment Induced Thrombocytopenia
Treatment Induced Cardiac Injury
Lead sponsor: The First Affiliated Hospital of Dalian Medical University
Sponsor class: OTHER
Collaborators: name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Anqing Municipal Hospital
name: Henan Cancer Hospital
name: Wuhan Union Hospital, China
name: Peking University Shougang Hospital
name: Chinese PLA General Hospital
name: Liaoning Cancer Hospital & Institute
name: Tianjin Medical University Cancer Institute and Hospital
name: Henan Provincial People's Hospital
name: Shanxi Provincial Cancer Hospital
name: Beijing Sanhuan Cancer Hospital
name: Hebei Medical University Fourth Hospital
name: Tongji Hospital
name: The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China
name: Bethune Charitable Foundation
First posted: 2022-06-09
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of an optimised dosing regimen of rhTPO's prophylactic treatment of cancer treatment-induced thrombocytopenia(CTIT) and to explore the cardioprotective effect of rhTPO in cancer patients with high risk of treatment-induced cardiac injury.

Detailed description: This is an open-label prospective randomized multicenter study of rhTPO's prophylactic treatment of CTIT in patients receiving chemotherapy at high risk of cardiac injury. Adult cancer patients with high risk of cancer treatment-induced thrombocytopenia and cardiac injury were enrolled. Patients will be randomised into the rhTPO treatment group or non-rhTPO treatment group with a 2:1 ratio. The patients in rhTPO group will receive rhTPO 300U/kg/d subcutaneous injection for 5 days per cycle and total 3 cycles. The primary endpoint is to observe the improvement of platelet count by rhTPO during 3 cycles treatment period.

Eligibility criteria: Inclusion Criteria:

* Males or females greater than or equal to 18 years of age at signing of the informed consent.
* Patients clinically judged to be at high risk of CTIT: Patients who had a platelet count below 50×10\^9/L in the past 3 months; or patients who meet the criteria for prophylactic treatment in the Chinese Expert Consensus on the Management of Thrombocytopenia due to Oncology Chemotherapy (2018 Edition).The criteria for prophylactic treatment include: 1) The nadir platelet value in the last chemotherapy cycle was \<50×10\^9/L；Or 2)The patients with nadir platelet value ≥50×10\^9/L and \<75×10\^9/L in the previous chemotherapy cycle also met at least one of the following risk factors for bleeding:

  1. With a previous history of bleeding.
  2. Chemotherapy regimens containing platinum, gemcitabine, cytarabine, anthracycline, etc.
  3. Combination regimens containing targeted or chemotherapy drugs which regularly result in thrombocytopenia.
  4. Thrombocytopenia caused by bone marrow infiltration of tumor cells.
  5. Eastern Cooperative Oncology Group (ECOG) score ≥2.
  6. Previous radiotherapy or ongoing radiotherapy, especially for long and flat bones (e.g. pelvis, sternum, etc.).
* Platelet count ≥75×10\^9/L and \<150×10\^9/L, Hemoglobin ≥9.0 g/dL and absolute neutrophils ≥1.5×10\^9 /L during screening.
* Patients with medium and high-risk with cardiotoxicity risk score (CRS) ≥3 and ECOG score of 0, 1, or 2 during screening.
* The current tumor treatment belongs to the scope of neoadjuvant, adjuvant, relapsed metastatic/advanced first-line and second-line therapies, anticipated to receive at least 2 cycles of current regimen with survival ≥ 6 months. The regimens may be 14-day, 21-day or 28-day cycles combined with targeted, immunotherapy, etc.
* Inclusion of organ tumours and lymphomas, with no restriction on the type and stage of organ tumours, etc.
* Patient provided signed informed consent

Exclusion Criteria:

* Patients with severe cerebrovascular disease (including but not limited to stroke, cerebrovascular accident, etc.) or serious heart disease (such as heart valve disease, arrhythmia, myocardial infarction, congenital heart disease, cardiomyopathy, heart failure, etc.) within the 3 months.
* Previous thrombocytopenia caused by non-oncology chemotherapy drugs within 6 months, including but not limited to primary immune thrombocytopenia, EDTA-dependent pseudo-thrombocytopenia, hypersplenism, etc.
* Patients with blood dysplasia-related diseases such as aplastic anemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndromes, etc.
* Patients with any arterial and venous thrombotic events within the past 6 months；
* Patients who had agents that increase platelet production or transfusion of platelets within the past 1 month.
* Abnormal liver function:

  * Patients without liver metastasis: ALT/AST \> 3ULN (upper limit of normal value) and TBIL \> 3ULN.
  * Patients with liver metastasis: ALT/AST≥5ULN, TBIL≥5ULN.
* Abnormal renal function: Scr≥1.5ULN or eGFR≤60ml/min.
* Patients with uncontrolled serious infection;
* Pregnant women or those planning to have children during the study period and breastfeeding patients.
* Any condition that the investigator considers inappropriate for inclusion in this study.

Primary outcomes:
measure: Proportion of patients whose platelet count is ≥ 75×10^9/L after 2 cycles cancer treatment.
timeFrame: After 2 cycles cancer treatment (month 1.5~month 2, depends on chemotherapy regimen), each cycle is 14, 21 or 28 days
Secondary outcomes:
measure: Proportion of patients receiving salvage treatment to increase platelet counts.
timeFrame: during 3 cycles cancer treatment period(each cycle is 14, 21 or 28 days)
measure: Changes in cTnT/cTnI
timeFrame: 1 and 3 months after initial treatment
measure: Changes in NT-proBNP
timeFrame: 1 and 3 months after initial treatment
measure: Changes in LVEF
timeFrame: 1 and 3 months after initial treatment
measure: Changes in neutrophile granulocyte count
timeFrame: during 3 cycles cancer treatment period(each cycle is 14, 21 or 28 days)
measure: Incidence of adverse events
timeFrame: from study start date to the end of follow-up, up to 3 months
Other outcomes:
Locations:
city: Anqing
country: China
facility: Anqing Municipal Hospital
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Chaoyang District Sanhuan Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Nanyang
country: China
facility: Affiliated Tumor Hospital of Nantong University
state: Jiangsu
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Xi'an
country: China
facility: Shaanxi Provincial Cancer Hospital
state: Shaanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: The First Affiliated Hospital of Dalian Medical University
name: Yunlong Xia, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: