Trial Title:
Hetrombopag for the Thrombocytopenia Induced by Concurrent Chemoradiotherapy
NCT ID:
NCT06433830
Condition:
Thrombocytopenia
Radiotherapy Side Effect
Conditions: Official terms:
Thrombocytopenia
Conditions: Keywords:
hetrombopag
thrombocytopenia
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Supportive Care
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Hetrombopag Olamine
Description:
The administration of hetrombopag as a monotherapy and at an initial dose of 7.5 mg
QD.The dose adjusted based on platelet count.
Arm group label:
Hetrombopag
Other name:
thrombopoietin receptor agonist
Summary:
Thrombocytopenia represents one of the main toxicities of concurrent chemoradiotherapy,
which may necessitate chemotherapy dose reductions, dose delays, or discontinuation, and
even compromise survival. Hetrombopag, a thrombopoietin receptor agonist, has shown
efficacy and safety in patients with chemotherapy-induced thrombocytopenia. However, the
efficacy of hetrombopag in patients who received concurrent chemoradiotherapy is not
clear yet. This study aimed to evaluate the efficacy and safety of hetrombopag in this
patient population.
Detailed description:
Antitumor related therapy is one of the common causes of thrombocytopenia. Chemotherapy
regimens based on drugs such as gemcitabine, platinum, anthracycline, and paclitaxel are
high-risk options for thrombocytopenia. The degree of thrombocytopenia caused by external
radiation therapy mainly depends on the irradiation dose, irradiation site, irradiation
field size, and irradiation duration. The synchronous radiotherapy and chemotherapy
regimen for head and neck tumors, esophageal cancer, rectal cancer, and other cancers
often involves platinum drugs, and the irradiation site often involves flat and irregular
bones. Therefore, the incidence of thrombocytopenia in patients during the treatment
process is higher than that of chemotherapy or radiotherapy alone. In a phase III
clinical study on the combination of carboplatin and paclitaxel in the treatment of
esophageal cancer, the incidence of thrombocytopenia was as high as 54%. Once
thrombocytopenia occurs, it may lead to a decrease in chemotherapy drug dosage, delay,
and cessation of radiotherapy and chemotherapy, and may require platelet infusion. In
follow-up studies of various cancer patients, it has been found that reducing the dosage
of chemotherapy drugs or delaying the chemotherapy cycle will reduce treatment efficacy
and lead to poor prognosis, including shortened disease-free survival (DFS) and overall
survival (OS) time.
TPO-RA drugs are currently approved for indications in the fields of chronic primary
immune thrombocytopenia (ITP), severe aplastic anemia (SAA), and chronic liver disease
(CLD). There are also relevant data reports in the CIT field. A phase II clinical study
using romiplostim for the treatment of CIT enrolled a total of 60 patients. After
treatment with romiplostim, 85% of patients returned to normal platelet count within 3
weeks and resumed chemotherapy. In the subsequent prescribed chemotherapy cycle, only
6.8% of patients experienced a relapse due to another round of chemotherapy. The
occurrence of CIT leads to a decrease or delay in chemotherapy dose; In another
randomized placebo-controlled phase II study using eltrombopag for the prevention of
solid tumor CIT, patients received gemcitabine monotherapy or gemcitabine combined with
cisplatin/carboplatin regimen chemotherapy, and treated with eltrombopag or placebo 100mg
before and 5 days after chemotherapy. In the 1-6 chemotherapy cycles, the average
platelet count on the day before chemotherapy in the eltrombopag group was numerically
higher than that in the placebo group, but did not reach statistically significant
differences. The incidence of grade 3/4 thrombocytopenia in the eltrombopag group was
lower than that in the placebo group. Among patients in the combination chemotherapy
group, the average time required for eltrombopag group to recover from the lowest
platelet count to normal was 8 days. The placebo group, on the other hand, requires 15
days, and the incidence of delayed/reduced chemotherapy dose or dose loss due to
thrombocytopenia is lower in patients in the eltrombopag group, Therefore, in gemcitabine
based chemotherapy, treatment with eltrombopag can shorten the time for platelet minimum
recovery and reduce the delayed/reduced chemotherapy dose caused by thrombocytopenia.
However, there is still a lack of stronger evidence-based medicine for the application of
TPO-RA drugs in CIT, and there is no relevant data in the field of concurrent
chemoradiotherapy induced thrombocytopenia.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years old, regardless of gender;
- Malignant tumor patients diagnosed through pathological or cytological examination,
regardless of cancer type, may experience thrombocytopenia during radical
synchronous radiotherapy and chemotherapy treatment;
- Platelet count of patients ≤ 75 × 10^9/L on the day or 3 days prior to enrollment;
- Expected survival time ≥ 12 weeks;
- ECOG PS score for physical condition: 0-2 points;
- The laboratory inspection indicators meet the following requirements:
1. Renal function: Cr ≤ ULN (upper limit of normal value) x 1.5, endogenous
creatinine clearance rate (Ccr) ≥ 55 ml/min;
2. Liver function: Total bilirubin ≤ ULN × 1.5; ALT and AST ≤ ULN × 3; (If it is
intrahepatic cholangiocarcinoma or liver metastasis, total bilirubin should not
exceed 3 times the normal upper limit, and transaminase should not exceed 5
times the normal upper limit);
- Women of childbearing age agree to use contraception during the study period and
within 6 months after the end of the study; And not a lactating patient; Male
patients who agree to contraception during the study period and within 6 months
after the end of the study;
- Those who have not participated in clinical trials of other drugs within the 4 weeks
prior to enrollment;
- It is expected that those with good compliance will be able to follow up on
therapeutic effects and adverse reactions according to the protocol requirements;
- No serious complications such as active gastrointestinal bleeding, perforation,
jaundice, gastrointestinal disorders Obstruction, non cancerous fever>38 °C;
- The subjects are able to understand the situation of this study and voluntarily sign
an informed consent form.
Exclusion Criteria:
- Screening for thrombocytopenia caused by non tumor treatment within the first 6
months, including but not limited to liver cirrhosis, splenic hyper function,
infection, and bleeding;
- Suffering from other hematopoietic system diseases besides thrombocytopenia caused
by concurrent radiotherapy and chemotherapy for malignant tumors, including
leukemia, primary immune thrombocytopenia, myeloproliferative diseases, multiple
myeloma, and myelodysplastic syndrome;
- Combined bone marrow invasion or bone marrow metastasis;
- After treatment with infusion of red blood cells or erythropoietin (EPO), hemoglobin
remains below 50g/L, or after treatment with granulocyte colony-stimulating factor
(G-CSF), the absolute value of neutrophils remains below 1.0 × 10^9/L;
- Have received pelvic and spinal radiation therapy, as well as bone field radiation,
within the three months prior to screening;
- History of arterial or venous thrombosis within the first 6 months of screening;
- Clinical manifestations of severe bleeding (such as gastrointestinal bleeding)
within the first two weeks of screening;
- Received platelet transfusion within 2 days prior to enrollment;
- Screening for patients with severe cardiovascular diseases (such as NYHA heart
function score III-IV), known arrhythmias that increase the risk of thromboembolism,
such as atrial fibrillation, coronary stent implantation, angioplasty, and coronary
artery bypass grafting within the first 6 months;
- Received treatment with recombinant human thrombopoietin (rhTPO), recombinant human
interleukin-11 (rhIL-11), or thrombopoietin receptor agonists (such as eltrombopag,
avatrombopag) within 14 days prior to screening;
- Patients who are known or expected to be allergic or intolerant to the active
ingredients or excipients of hetrombopag tablets (excipients include cellulose
lactose, low substituted hydroxypropyl cellulose, magnesium stearate, and film
coated premixes);
- Breastfeeding women;
- Vulnerable groups, including individuals with mental illness, cognitive impairment,
critically ill patients, minors, pregnant women, etc;
- The researcher believes that the participants are not suitable for enrollment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310016
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaonan Sun
Phone:
(+86)-0571-86006783
Email:
sunxiaonan@zju.edu.cn
Contact backup:
Last name:
Weiwen Zhou
Phone:
(+86)-0571-86006783
Email:
21718403@zju.edu.cn
Start date:
May 10, 2022
Completion date:
July 30, 2025
Lead sponsor:
Agency:
Sir Run Run Shaw Hospital
Agency class:
Other
Source:
Sir Run Run Shaw Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06433830
