Overview

Penpulimab Plus Chemotherapy With/Without Anlotinib for Patients With Advanced Esophageal Squamous Cell Carcinoma

Status:
Not yet recruiting
Trial end date:
2024-07-01
Target enrollment:
0
Participant gender:
All
Summary
Penpulimab plus chemotherapy with or without Anlotinib as first-line therapy for patients with advanced esophageal squamous cell carcinoma (Answer): A randomized two-arm clinical study.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Nanfang Hospital of Southern Medical University
Treatments:
Albumin-Bound Paclitaxel
Cisplatin
Paclitaxel
Criteria
Inclusion Criteria:

1. Patients with advanced metastatic esophageal squamous cell carcinoma who cannot
receive radical treatment (excluding mixed adenosquamous carcinoma);

2. Those who have not received systemic treatment in the past, or (new) adjuvant
treatment/radical surgery/radical radiotherapy and chemotherapy have relapsed for more
than 6 months; Note: Including patients with advanced or recurring non-target lesions
who have progressed again after radiotherapy alone. For local lesions (non-target
lesions), the time from the end of palliative treatment to the enrollment time> 2
weeks;

3. According to the RECIST 1.1 version of the curative effect evaluation standard for
solid tumors, there is at least one measurable lesion; the measurable lesion should
not have received local treatment such as radiotherapy (the lesion located in the
previous radiotherapy area, if it is confirmed that it has progressed, and meets
RECIST1.1 Standard, target lesions can also be selected);

4. Patients between 18 and 75 years old;

5. ECOGPS score: 0~1 points; the expected survival period is more than 3 months;

6. Tumor specimens can be provided to determine gene detection and PD-L1 expression, at
least 15 white sheets (assessed by the company); provide two oral swabs; within 7 days
before the medication, the first, third, and sixth at the end of the cycle, one tube
of 6ml EDTA anticoagulant blood will be provided.

7. It has sufficient organ and bone marrow function, that is, it meets the following
standards:

(1) The standard of routine blood examination must meet: Hemoglobin content (HB) ≥90g/L (no
blood transfusion within 28 days); Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet
count (PLT) ≥100×109/L. (2) The biochemical inspection shall meet the following standards:
Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); ALT and
AST≤2.5´ULN; if there is liver metastasis, ALT and AST≤5´ULN; Cr≤1.5´ULN or creatinine
clearance (CCr)≥60ml/min; (Cockcroft-Gault formula) (3) The coagulation function is
adequate, which is defined as the international normalized ratio (INR) or prothrombin time
(PT) ≤ 1.5 times ULN; 8) Women of childbearing age must take appropriate contraceptive
measures from screening to 3 months after stopping the treatment, and they must be
non-lactating patients. Before starting the administration, the pregnancy test is negative,
or meeting one of the following criteria proves that there is no risk of pregnancy:

1. Post-menopausal is defined as amenorrhea at least 12 months after the age is greater
than 50 years and all exogenous hormone replacement therapy is stopped;

2. For women younger than 50 years old, if the amenorrhea is 12 months or more after
stopping all exogenous hormone treatments, and the levels of luteinizing hormone (LH)
and follicle stimulating hormone (FSH) are within the laboratory postmenopausal
reference value range, also Can be considered post-menopausal;

3. Have received irreversible sterilization, including hysterectomy, bilateral
ovariectomy or bilateral fallopian tube resection, except for bilateral tubal
ligation.

For men, they must agree to use appropriate methods of contraception or have been
surgically sterilized during the trial period and 8 weeks after the last trial drug
administration; 9) The patient voluntarily joined the study, signed an informed consent
form, had good compliance, and cooperated with the follow-up.

Exclusion Criteria:

1. It is known that esophageal squamous cell carcinoma tends to be completely obstructed
under endoscopy and requires interventional treatment to relieve the obstruction;

2. Patients with ulcerative esophageal squamous cell carcinoma;

3. Patients who have a higher risk of bleeding or perforation due to the tumor's obvious
invasion of the adjacent organs (aorta or trachea) of the esophageal lesion, or
patients who have formed a fistula;

4. Patients with esophageal squamous cell carcinoma whose esophageal lesions have not
been reduced after radiotherapy without surgical resection of the primary lesion;

5. Allergy to paclitaxel and cisplatin preparations or excipient ingredients;

6. Patients who have used paclitaxel or cisplatin in adjuvant chemotherapy and have
relapsed or metastasized within six months; Note: Those who have relapsed or
metastasized for more than six months can be included in the study;

7. Previously received anti-tumor immunotherapy (including immune checkpoint inhibitors,
immune cell therapy, etc.) or anti-angiogenesis targeted therapy drugs (including
antibodies and small molecule tyrosine kinase inhibitors);

8. There are many factors that affect oral medications (such as inability to swallow,
chronic diarrhea, intestinal obstruction, etc.), but patients who have difficulty
swallowing and can drink, can take Anlotinib after dissolving the granules;

9. The burden of liver metastases accounts for more than 50% of the entire liver volume;

10. Patients with any severe and/uncontrolled diseases, including:

1. Patients with unsatisfactory blood pressure control using antihypertensive drugs
(systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg); patients
with grade II or higher myocardial ischemia or myocardial infarction, arrhythmia
(including QT interval ≥480ms); according to NYHA standards , Grade III-IV
cardiac insufficiency, or cardiac color Doppler ultrasound examination reveals
that the left ventricular ejection fraction (LVEF) is less than 50%;

2. Active or uncontrolled serious infection;

3. Liver diseases such as cirrhosis, decompensated liver disease, chronic active
hepatitis;

4. Poor control of diabetes (fasting blood glucose (FBG)> 10mmol/L);

5. Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein
content is confirmed to be greater than 1.0g;

11. Long-term unhealed wounds or fractures;

12. Patients with esophageal squamous cell carcinoma with active bleeding within 2 months
of the primary lesion; pulmonary hemorrhage with NCICTCAE grade> grade 1 occurred
within 4 weeks before enrollment; other sites with NCICTCAE grade> grade 2 occurred
within 4 weeks before enrollment Bleeding; patients with bleeding tendency (such as
active peptic ulcer) or who are receiving thrombolytic or anticoagulant therapy such
as warfarin, heparin or their analogues;

13. Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first
dose of the study or expected major surgery during the study treatment period.

14. A history of gastrointestinal perforation and/or fistula in the 6 months before the
enrollment treatment; or arteriovenous thrombotic events, such as cerebrovascular
accidents (including temporary ischemic attacks), deep vein thrombosis and lungs
Embolizer

15. There are known symptomatic central nervous system metastases and/or cancerous
meningitis;

16. Ascites with clinical significance, including any ascites that can be found on
physical examination, ascites that has been treated in the past or still needs to be
treated at present, only those with a small amount of ascites but asymptomatic on
imaging can be selected;

17. Patients with moderate pleural effusion on both sides, or large pleural effusion on
one side, or patients who have caused respiratory dysfunction and require drainage;

18. Known to have active tuberculosis;

19. Suffer from interstitial lung disease that requires steroid therapy;

20. Uncontrolled metabolic disorders or other non-malignant tumor organs or systemic
diseases or cancer secondary reactions, which may lead to higher medical risks and/or
uncertainty in survival evaluation;

21. Patients with significant malnutrition, BMI<13.6kg/m2;

22. People who have a history of psychotropic drug abuse and cannot be quit or have mental
disorders;

23. Have a history of immunodeficiency, including those who have tested positive for HIV
or have other acquired or congenital immunodeficiency diseases, or have a history of
organ transplantation;

24. History of other primary malignant tumors, except for the following: 1) Malignant
tumors that have been completely remitted for at least 2 years before enrollment and
no other treatment is required during the study period; 2) Non-melanoma skin that has
been adequately treated and has no evidence of disease recurrence Carcinoma or
malignant freckle-like nevus; 3) Carcinoma in situ that has been adequately treated
and has no evidence of disease recurrence;

25. Female patients who are pregnant or breastfeeding;

26. According to the judgment of the investigator, those with concomitant diseases that
seriously endanger the safety of the patient or affect the patient's completion of the
study.