Trial Title:
Neoadjuvant Therapy of Anlotinib Combined With Toripalimab and Chemotherapy for Resectable Esophageal Carcinoma
NCT ID:
NCT05996484
Condition:
Esophageal Carcinoma
Neoadjuvant Therapy
Conditions: Official terms:
Carcinoma
Esophageal Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
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:
Toripalimab
Description:
Toripalimab, 240mg, IV., D1, every 3 weeks, 4 cycles.
Arm group label:
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Other name:
JS001
Intervention type:
Drug
Intervention name:
Anlotinib hydrochloride
Description:
Anlotinib Hydrochloride is a capsule in the form of 8 mg ,10 mg and 12 mg, orally, once
daily, 2 weeks on/1 week off, every 3 weeks, 4 cycles.
Arm group label:
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Other name:
Anlotinib
Intervention type:
Drug
Intervention name:
Albumin paclitaxel
Description:
Albumin paclitaxel, 200-260 mg/m2, IV., D1, every 3 weeks, 4 cycles.
Arm group label:
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Other name:
Paclitaxel For Injection (Albumin Bound)
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin, 60-75 mg/m2, IV., D1, every 3 weeks, 4 cycles.
Arm group label:
Neoadjuvant Anlotinib Combined With Toripalimab and Chemotherapy
Other name:
CDDP
Summary:
The purpose of this study is to explore the effectiveness and safety of the combination
of Anlotinib, Toripalimab, and albumin-bound paclitaxel with cisplatin for neoadjuvant
therapy in resectable esophageal squamous cell carcinoma. The study aims to improve the
pathological complete response rate (pCR), R0 resection rate, and disease-free survival
(DFS) in patients undergoing esophageal cancer surgery. The findings of this study will
provide guidance and new options for the treatment of locally advanced esophageal cancer
patients.
Detailed description:
Both anti-angiogenic therapy and immune checkpoint inhibitors have shown preliminary
efficacy and safety data in the field of neoadjuvant therapy for esophageal cancer.
However, there is currently no available data on the combination of immune checkpoint
inhibitors, anti-angiogenic therapy, and chemotherapy in neoadjuvant therapy for
esophageal cancer. Based on the favorable survival benefits of this combination in
first-line and second-line treatments for multiple tumors, we aim to explore another
neoadjuvant treatment approach - adding anti-angiogenic agents to immune checkpoint
inhibitor-based neoadjuvant therapy, providing a new perioperative treatment strategy for
esophageal cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age range: 18-70 years, both male and female.
2. Patients with histopathological diagnosis of esophageal squamous cell carcinoma
confirmed by gastroscopy/ultrasound gastroscopy, and clinical diagnosis of cT2N1-2M0
or cT3N0-2M0, with TNM staging of stage II-III B.
3. Non-cervical esophageal cancer patients.
4. No prior systemic or local treatment for esophageal cancer, with at least one
measurable lesion for imaging evaluation of neoadjuvant therapy according to RECIST
1.1 criteria.
5. ECOG PS (Eastern Cooperative Oncology Group Performance Status): 0-1.
6. Estimated survival period ≥12 months.
7. Subjects without significant dysfunction of major organs, with normal assessment of
thyroid, lung, liver, kidney, and cardiac function.
8. Reproductive-age women must have taken reliable contraceptive measures or undergone
pregnancy testing (serum or urine) within 7 days prior to enrollment, with negative
results, and be willing to use appropriate contraception during the trial and for 8
weeks after the last administration of the investigational drug. For males, they
must agree to use appropriate contraception during the trial and for 8 weeks after
the last administration of the investigational drug, or have undergone surgical
sterilization.
9. Subjects voluntarily participate in this study, sign an informed consent form,
demonstrate good compliance, adhere to the planned schedule for regular clinical
follow-up and necessary treatment, and cooperate in obtaining regular blood and
tissue samples.
Exclusion Criteria:
1. Patients who have had or currently have other malignant tumors within the past 1.5
years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and
superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1
(tumor invades lamina propria)].
2. Patients with ulcerative esophageal squamous cell carcinoma.
3. Patients with esophageal fistula or tracheal fistula.
4. Patients allergic to anlotinib, toripalimab, or albumin-bound paclitaxel.
5. Patients with a history of immunodeficiency diseases, including HIV-positive
patients or those with other acquired or congenital immunodeficiency diseases, or a
history of organ transplantation.
6. Patients with severe and/or uncontrolled diseases are excluded from the study,
including:
6.1 Patients with unsatisfactory blood pressure control (systolic blood pressure
≥160 mm Hg or diastolic blood pressure ≥100 mmHg).
6.2 Patients with grade I or higher myocardial ischemia or myocardial infarction.
6.3 Patients with arrhythmia (including QT interval ≥480 ms) and grade I heart
failure.
6.4 Patients with poorly controlled diabetes (fasting blood glucose >10 mmol/L) or
receiving high-dose glucocorticoid therapy.
6.5 Patients with active or uncontrolled severe infections. 6.6 Patients with
decompensated liver disease, active hepatitis B (HBV-DNA ≥10^4 copies/ml or 2000
IU/ml), or hepatitis C (positive for hepatitis C antibodies and HCV RNA) exceeding
the lower limit of the analytical method.
6.7 Patients with hyperthyroidism or hypothyroidism. 6.8 Patients with active
tuberculosis.
7. Unresolved toxicities of grade 2 or higher, excluding alopecia, caused by any prior
treatment.
8. Individuals with multiple factors that affect oral medication administration, such
as dysphagia, chronic diarrhea, and intestinal obstruction.
9. Individuals with urine routine showing urinary protein ≥++, and confirmed 24-hour
urine protein quantification >1.0 g.
10. Individuals who underwent major surgical treatment, incisional biopsy, or
significant traumatic injury within 28 days prior to randomization.
11. Abnormal coagulation function: INR >1.5 or prothrombin time (PT) > ULN + 4 seconds
or APTT > 1.5 ULN, with a bleeding tendency or receiving thrombolytic or
anticoagulation therapy. Patients who experienced any bleeding or hemorrhagic events
≥ grade 3 CTCAE within 4 weeks prior to randomization, with unhealed wounds, ulcers,
or fractures.
12. Occurrence of arterial/venous thrombotic events within 6 months, such as
cerebrovascular accidents (including transient ischemic attacks), deep vein
thrombosis, and pulmonary embolism.
13. Pregnant or lactating women.
14. Presence of distant metastasis.
15. Patients with significant bone marrow suppression.
16. Patients with mental illness or a history of substance abuse with psychotropic
drugs.
17. Patients who participated in other drug clinical trials within 4 weeks.
18. Patients with accompanying diseases that, in the investigator's judgment, pose a
serious risk to patient safety or may affect the patient's completion of the study.
19. Patients with inherited bleeding tendencies, coagulation disorders, potential
invasion of major blood vessels, and other bleeding risks, who experienced
clinically significant bleeding symptoms or had a clear bleeding tendency with
gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood ++
and above within 3 months prior to enrollment.
20. Patients deemed unsuitable
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
September 2023
Completion date:
July 2026
Lead sponsor:
Agency:
Nanfang Hospital, Southern Medical University
Agency class:
Other
Source:
Nanfang Hospital, Southern Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05996484
