An Exploratory Phase II Clinical Trial of Anlotinib Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Hydrochloride anlotinib
- Conditions
- To Evaluate the Efficacy and Safety of Anlotinib Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Cervical Cancer
- Sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Enrollment
- 36
- Primary Endpoint
- 12 months Recurrence-free Survival Rate
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the visit;
- •Age ≥ 18 years old (calculated on the date of signing the informed consent);
- •Patients with cervical cancer confirmed by pathology or histology, including squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, and small cell neuroendocrine carcinoma;
- •Treatment-naïve patients (have not received local treatment or systemic treatment);
- •Locally advanced patients who plan to receive concurrent chemoradiotherapy, FIGO IB3, IIA2-IVA stage (unable/not suitable for pelvic exenteration);
- •There are measurable lesions defined by RECIST standard v1.1;
- •ECOG score 0-1;
- •Expected survival time ≥ 3 months;
- •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;
- •The main organ function is good, and the inspection indicators within 14 days before enrollment meet the following requirements:
Exclusion Criteria
- •Patients with known hypersensitivity to anti-angiogenic drugs or their excipients;
- •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;
- •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);
- •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;
- •CTCAE ≥ grade 1 (5.0 standard) unresolved toxic reactions caused by any previous treatment, but excluding hair loss;
- •People with multiple factors that affect oral medication (such as inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.);
- •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;
- •There is third space effusion (such as pleural effusion, ascites, pericardial effusion) that cannot be controlled by drainage or other methods;
- •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);
- •Patients with any severe and/or uncontrolled disease, including:
Arms & Interventions
Anlotinib+TP then CCRT+Anlotinib
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
Intervention: Hydrochloride anlotinib
Anlotinib+TP then CCRT+Anlotinib
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
Intervention: cis Platinum/carboplatin
Anlotinib+TP then CCRT+Anlotinib
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
Intervention: External beam radiotherapy and brachytherapy
Outcomes
Primary Outcomes
12 months Recurrence-free Survival Rate
Time Frame: 1 years from enrollment
Proportion of participants free of tumor recurrence 12 months after enrollment
Secondary Outcomes
- Progression-free Survival(2 years from enrollment)
- Objective Response Rate(2 years from enrollment)
- Overall Survival(2 years from enrollment)
- Adverse events(2 years from enrollment)
- Tumor marker complete response rate(1 years from enrollment)