Trial Title:
Anlotinib Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Cervical Cancer
NCT ID:
NCT05772377
Condition:
To Evaluate the Efficacy and Safety of Anlotinib Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Cervical Cancer
Conditions: Official terms:
Uterine Cervical Neoplasms
Carboplatin
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Hydrochloride anlotinib
Description:
Hydrochloride anlotinib is a small molecular anti-angiogenesis drug with multiple
targets. It will be taken at a starting dose of 10 mg for 14 days. Then participants will
rest for 7 days and start a new cycles. At most of 3 cycles will be administrated. If
intolerable toxicity happen, dosage of 8mg will be taken.
Arm group label:
Anlotinib+TP then CCRT+Anlotinib
Intervention type:
Drug
Intervention name:
cis Platinum/carboplatin
Description:
Concurrent chemotherapy with cisplatin at 75mg/m2 during radiotherapy will be the most
preferred regimen. For patients who cannot tolerate the toxicity of cisplatin, 75 mg/m2
nedaplatin will be used as an alternative drug.
Arm group label:
Anlotinib+TP then CCRT+Anlotinib
Intervention type:
Radiation
Intervention name:
External beam radiotherapy and brachytherapy
Description:
Radiation will be given by external beam of 40Gy total dose and 3D-brachytherapy of
30Gy/2.5F. Duration of radiotherapy will be no more than 5 weeks
Arm group label:
Anlotinib+TP then CCRT+Anlotinib
Summary:
To observe the efficacy and safety of hydrochloride anlotinib combined with concurrent
radiochemotherapy for patients with FIGO stage IB3 and IIA2-IVA cervical cancer.
Detailed description:
Subjects received "anlotinib + paclitaxel/cisplatin" induction therapy for two cycles,
and then received "anlotinib + concurrent chemoradiotherapy, sequential high-dose-rate
intracavitary radiotherapy, sequential chemotherapy consolidation therapy"
regimen:Induction regimen:Anlotinib: 10 mg, po, qd, d1-d14, q3w, 2 consecutive cycles
Paclitaxel 175mg/m2 intravenous injection for 3 hours, d1 Cisplatin 75mg/m2, iv, divided
into 3 days, q3w;Unable to tolerate, nedaplatin 75mg/m2, iv, d1 can be used instead;21
days as a cycle, a total of 2 cycles
Treatment programs:
Anlotinib: 10 mg, po, qd, d1-d14, q3w, 2 consecutive cycles；Cisplatin: 30-35 mg/m2, iv,
d1, qw, 5 consecutive cycles；Pelvic external radiation therapy: once a day, 1.8-2
Gy/time, 5 days a week, for 5 consecutive weeks, a total of 45-50 Gy sequential；High dose
rate intracavitary radiotherapy: 6 Gy/time, twice a week, 5 consecutive times, a total of
30 Gy/2.5 weeks, bioequivalent dose of 40 Gy sequential；Taxane drugs: including but not
limited to paclitaxel, nab-paclitaxel, paclitaxel liposome, etc. The dosage regimen is
determined by the investigator;Cisplatin 75mg/m2, iv, divided into 3 days, q3w;Unable to
tolerate, nedaplatin 75mg/m2, iv, d1 can be used instead;2 cycles.A total of 36 patients
will be included and this study will be conducted in the department of radiation and
clinical oncology in The First Affiliated Hospital of Nanjing Medical University.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. The subjects voluntarily joined the study, signed the informed consent form,
had good compliance, and cooperated with the visit; 2. Age ≥ 18 years old
(calculated on the date of signing the informed consent); 3. Patients with
cervical cancer confirmed by pathology or histology, including squamous cell
carcinoma, adenocarcinoma, adenosquamous carcinoma, and small cell
neuroendocrine carcinoma; 4. Treatment-naïve patients (have not received local
treatment or systemic treatment); 5. Locally advanced patients who plan to
receive concurrent chemoradiotherapy, FIGO IB3, IIA2-IVA stage (unable/not
suitable for pelvic exenteration); 6. There are measurable lesions defined by
RECIST standard v1.1; 7. ECOG score 0-1; 8. Expected survival time ≥ 3 months;
9. For non-lactating patients, the serum or urine pregnancy test was negative
within 7 days before the study enrollment; female subjects of childbearing age
must agree to use high-efficiency methods of contraception during the study
period and within 6 months after the last administration of the study drug; 10.
The main organ function is good, and the inspection indicators within 14 days
before enrollment meet the following requirements:
1. Blood routine examination (without blood transfusion within 14 days):
1. Hemoglobin (HB) ≥ 90 g/L;
2. Neutrophil count (ANC) ≥ 1.5×109/L;
3. Platelet count (PLT) ≥ 80×109/L;
2. Biochemical examination:
1. Total bilirubin ≤ 1.5×ULN (upper limit of normal value);
2. Blood alanine aminotransferase (ALT) and blood aspartate aminotransferase
(AST) ≤ 2.5×ULN; if there is liver metastasis, ALT and AST ≤ 5×ULN;
3. Serum creatinine (Cr) ≤ 1.5ULN or creatinine clearance ≥ 60mL/min
(Cockcroft-Gault formula);
3. Blood coagulation function test:
1. Activated partial thromboplastin time (APTT), international normalized
ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN;
2. Doppler ultrasound evaluation: left ventricular ejection fraction (LVE F)
≥ 50%;
Exclusion Criteria:
-
1. Patients with known hypersensitivity to anti-angiogenic drugs or their
excipients; 2. Patients with other malignant tumors (except cured carcinoma in
situ of the cervix, papillary thyroid carcinoma, basal cell carcinoma of the
skin or squamous cell carcinoma of the skin) currently or within the past 5
years; 3. Received radiotherapy, chemotherapy, surgical treatment (excluding
local puncture), molecular targeted therapy, immunotherapy or participated in
any other drug clinical research within 4 weeks (28 days) before screening
(enrolment) or are receiving other clinical trials Study-treated patients
(except patients who were followed up for overall survival in a study); 4.
Patients with previous or current central nervous system metastases or
leptomeningeal disease. Remarks: If the subject has completed radiotherapy or
surgery for CNS metastases > 4 weeks before study enrollment, and the subject's
nervous system is stable for ≥ 4 weeks (that is, no new neurological deficits
caused by brain metastases are found at the time of screening) , central
nervous system imaging examination did not find new lesions, and do not need
glucocorticoids/steroids for treatment), you can participate in this study; 5.
CTCAE ≥ grade 1 (5.0 standard) unresolved toxic reactions caused by any
previous treatment, but excluding hair loss; 6. People with multiple factors
that affect oral medication (such as inability to swallow,
post-gastrointestinal resection, chronic diarrhea and intestinal obstruction,
etc.); 7. Imaging studies show that the tumor has invaded around important
blood vessels or the researchers judged that the tumor is very likely to invade
important blood vessels during the follow-up study and cause fatal massive
hemorrhage; 8. There is third space effusion (such as pleural effusion,
ascites, pericardial effusion) that cannot be controlled by drainage or other
methods; 9. Abnormal coagulation function (INR>1.5 or prothrombin time
(PT)>ULN+4 seconds or APTT>1.5 ULN), bleeding tendency or receiving
thrombolytic or anticoagulant therapy; Note: On the premise that the
international normalized ratio (INR) of prothrombin time is ≤1.5, the use of
low-dose heparin (daily dosage of 0.6-12,000 U for adults) or low-dose aspirin
(daily dosage of ≤ 100 U) is allowed for prophylactic purposes. mg); 10.
Patients with any severe and/or uncontrolled disease, including:
1. Patients with hypertension who cannot be well controlled by a single
antihypertensive drug treatment (systolic blood pressure > 150 mmHg, diastolic
blood pressure > 90 mmHg);
2. Those with a history of unstable angina; newly diagnosed with angina within 3
months before screening or myocardial infarction within 6 months before
screening; arrhythmia (including QTcF: male ≥ 450 ms) requires long-term use of
antiarrhythmics Drugs and New York Heart Association grade ≥ II cardiac
insufficiency;
3. Active or uncontrolled severe infection (≥CTCAE 5.0 grade 2 infection);
4. Those with a history of immunodeficiency, including those who are HIV positive
or suffer from other acquired or congenital immunodeficiency diseases, or have
a history of organ transplantation;
5. Poorly controlled diabetes (fasting blood glucose (FBG) > 10mmol/L);
6. Urine routine prompts urine protein ≥ ++, and confirmed 24-hour urine protein
quantity > 1.0g;
7. Patients who have epileptic seizures and need treatment; 11. Regardless of the
severity, patients with any bleeding constitution or medical history; within 4
weeks before enrollment, patients with any bleeding or bleeding events CTCAE ≥
grade 3 (5.0 standard), with unhealed wounds, ulcers or fractures; 12. Patients
with excessive arterial/venous thrombosis events before enrollment or within 6
months, such as cerebrovascular accidents (including transient ischemic
attacks), deep vein thrombosis and pulmonary embolism; 13. Patients with a
clear history of neurological or mental disorders, including epilepsy or
dementia; 14. Female patients who are pregnant or breastfeeding, female
patients who are fertile and have a positive baseline pregnancy test, or female
patients of childbearing age who are unwilling to take effective contraceptive
measures throughout the trial period; 15. According to the investigator's
judgment, there are concomitant diseases that seriously endanger the safety of
patients or affect the completion of the study;
Gender:
Female
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Start date:
July 1, 2023
Completion date:
June 1, 2025
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05772377
