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

NCT05214222 | Recruiting Phase 2

• 1 other identifier: NFEC-2021-405
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Esophageal Squamous Cell Carcinoma

Keywords

PD-1 inhibitor/anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1

  up to approximately 2 year

Secondary Outcomes (9)

• Disease Control Rate (DCR)

  up to approximately 2 year

• Progression Free Survival (PFS) include PFS1,PFS2

  up to approximately 2 year

• Overall Survival (OS)

  up to approximately 3 year

• Safety: AE

  up to approximately 2 year

• Change From Baseline in Health-related Quality of life (HRQoL) Score Using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)

  up to approximately 2 year

Study Arms (2)

group A

EXPERIMENTAL

Penpulimab plus chemotherapy with Anlotinib

Drug: Anlotinib/Penpulimab/Chemotherapy

group B

EXPERIMENTAL

Penpulimab plus chemotherapy

Drug: Penpulimab/Chemotherapy

Interventions

Anlotinib/Penpulimab/Chemotherapy DRUG

Initial treatment (4-6 cycles): Anlotinib, Penpulimab, Paclitaxel or Albumin Paclitaxel,Cisplatin * Anlotinib: once a day, 1 capsule each time (10mg for body weight \<60KG, 12mg for body weight ≥60KG), d1-d14, 3 weeks as a treatment cycle. * Penpulimab: 200 mg, d1 per cycle, once every 3 weeks. * Paclitaxel: According to 135-175mg/m2, intravenous infusion\> 2h, d1, 3 weeks as a treatment cycle; Albumin paclitaxel: According to 200-260mg/m2, intravenous infusion for 30 minutes, d1, 3 weeks as a treatment cycle. * Cisplatin: 60-75mg/m2, intravenous infusion, divided into d1-d3 medication per cycle; 3 weeks is a treatment cycle. Maintenance treatment: Anlotinib, Penpulimab * Anlotinib: once a day, 1 capsule each time (the same as the initial treatment dose), take the drug every cycle d1-d14, 3 weeks as a treatment cycle. * Penpulimab: 200mg, d1 per cycle, once every 3 weeks

Also known as: Anlotinib, Penpulimab, Paclitaxel or Albumin Paclitaxel,Cisplatin

group A

Penpulimab/Chemotherapy DRUG

Initial treatment (4-6 cycles): Penpulimab, Paclitaxel or Albumin Paclitaxel,Cisplatin * Penpulimab: 200 mg, d1 per cycle, once every 3 weeks. * Paclitaxel: According to 135-175mg/m2, intravenous infusion\> 2h, d1, 3 weeks as a treatment cycle; Albumin paclitaxel: According to 200-260mg/m2, intravenous infusion for 30 minutes, d1, 3 weeks as a treatment cycle. * Cisplatin: 60-75mg/m2, intravenous infusion, divided into d1-d3 medication per cycle; 3 weeks is a treatment cycle. Maintenance treatment: Penpulimab • Penpulimab: 200mg, d1 per cycle, once every 3 weeks Post-progression genetic testing, continued treatment: Anlotinib,Penpulimab Anlotinib: Once daily, one capsule per time (10mg for weight \<60KG, 12mg for weight ≥60KG), administered from day 1 to day 14 of each cycle. Two consecutive weeks of treatment followed by one week off, 3 weeks per treatment cycle. Penpulimab: 200mg, administered on day 1 of each cycle, every 3 weeks.

Also known as: Penpulimab, Paclitaxel or Albumin Paclitaxel,Cisplatin

group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stage III-IV esophageal squamous cell carcinoma who are not candidates for curative treatment (excluding adenosquamous carcinoma mixed type);
• 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;
• 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);
• Patients between 18 and 75 years old;
• ECOGPS score: 0\~1 points; the expected survival period is more than 3 months;
• 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.
• 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) ≥1.5×10\^9/L; Platelet count (PLT) ≥100×10\^9/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:
• 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;
• 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;
• 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.

You may not qualify if:

• It is known that esophageal squamous cell carcinoma tends to be completely obstructed under endoscopy and requires interventional treatment to relieve the obstruction;
• Patients with ulcerative esophageal squamous cell carcinoma;
• 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;
• Patients with esophageal squamous cell carcinoma whose esophageal lesions have not been reduced after radiotherapy without surgical resection of the primary lesion;
• Allergy to paclitaxel and cisplatin preparations or excipient ingredients;
• 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;
• 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);
• 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;
• The burden of liver metastases accounts for more than 50% of the entire liver volume;
• Patients with any severe and/uncontrolled diseases, including:
• 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%;
• Active or uncontrolled serious infection;
• Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;
• Poor control of diabetes (fasting blood glucose (FBG)\> 10mmol/L);
• Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein content is confirmed to be greater than 1.0g;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Interventions

anlotinib; penpulimab; Paclitaxel; Cisplatin; Drug Therapy

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• wei wang

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

wei wang

CONTACT

020-61642136; wwei9500@smu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2022
• First Posted: January 28, 2022
• Study Start: September 2, 2022
• Primary Completion (Estimated): June 2, 2026
• Study Completion (Estimated): September 2, 2028
• Last Updated: December 30, 2024

Record last verified: 2024-12

Locations

CN (1)