Endostar Combined With Paclitaxel and Nedaplatin in Treating Patients With Recurrent or Metastatic Esophageal Cancer

Phase 2

Completed

• Conditions: Esophageal Squamous Cell Carcinoma
• Interventions: Drug: Paclitaxel+Nedaplatin+Endostar

• Registration Number: NCT02350517
• Lead Sponsor: Yuhong Li

Brief Summary

This phase Ⅱ study was designed to evaluate the efficacy and safety of endostar combined with paclitaxel and nedaplatin as first-line therapy in treating patients with recurrent or metastatic esophageal squamous cell cancer.

Detailed Description

The prognosis of recurrent or metastatic esophageal squamous cell cancer is poor. However, there is still no standard chemotherapy regimen recommended for this disease because of the lack of trails. Currently, anti-angiogenesis therapy had been proved to improve the survival successfully in colorectal cancer, non-small cell lung cancer, breast cancer, glioma and kidney cancer. Recent studies showed that the high level of VEGF was negative correlated with the prognosis of esophageal cancer. Endostar, as a novel endogenous angiogenesis inhibitors, was proved to significantly inhibited the proliferation and metastasis in esophageal cell lines and animal models. A retrospective study also reported the safety and efficacy of the combination therapy of paclitaxel liposome and recombinant human endostatin. Based on the basis above, we designed this phase Ⅱ study to evaluate the efficacy and safety of endostar combined with paclitaxel and nedaplatin as first-line therapy in treating patients with recurrent or metastatic esophageal squamous cell cancer.

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-24
• Study First Submitted QC: 2015-01-24
• Study First Posted: 2015-01-29
• Primary Completion: 2019-12
• Study Completion: 2022-12
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• Patients have provided a signed Informed Consent Form

• Age: 18-75 years old

• Histologically confirmed diagnosis of recurrent or metastatic or unresectable advanced esophageal squamous cell carcinoma

• Patients have neither received any palliative chemotherapy nor adjuvant chemotherapy or concurrent chemotherapy with taxane based drugs or large doses cisplatin (cumulative dose ≥ 300mg/m2). The time from the last adjuvant or concurrent chemotherapy to relapse or metastasis should more than 6 months.

• Measurable disease in at least 1 diameter by CT scan or MRI as per RECIST 1.1 criteria; Targeted lesions should not include primary esophageal lesions

• Life expectancy ≥ 3 months

• Karnofsky score ≥70

• Patient has adequate bone marrow and organ function

  • Leukocyte ≥ 3.5 x 10^9/L
  • eAbsolute Neutrophil Count (ANC) ≥ 1.8 x 10^9/L
  • Platelets ≥ 90 x 10^9/L
  • Hemoglobin ≥ 10g/L

• Patient has adequate liver function

  • AST and ALT not more than 2.5 times ULN (not more than 5.0 times ULN if there is liver metastasis)
  • Serum bilirubin ≤ 1.2 x ULN
  • Creatinine ≤ 1.2 times ULN
  • Alkaline phosphatase ≤ 5.0 times ULN

• No serious complications such as active gastrointestinal hemorrhage, perforation, jaundice, gastrointestinal obstruction, non cancerous fever > 38 ℃.

• Patients with effective contraceptive measures

• Expect good compliance

Exclusion Criteria

• Patients have received radiotherapy in 3 months.
• Patients with relapse recurrent or metastatic lesions in radiated area.
• Patient has received previous treatment with VEGF inhibitors
• Known severe hypersensitivity to the drugs in the experimental chemotherapy or any of the excipients of these products
• Patients without measureable lesions
• Severe systemic disease out of control such as unstable or uncompensated respiratory,cardiac,liver,renal diseases
• Patients with chronic diarrhea
• Patient has a concurrent malignancy or has a malignancy within 5 years of study enrollment (with the exception of nonmelanoma skin cancer or cervical carcinoma in situ
• psychiatric illness including CNS metastases that would prevent the patient from giving informed consent
• Pregnant or lactating women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Paclitaxel+Nedaplatin+Endostar	Paclitaxel+Nedaplatin+Endostar	Patients will receive chemotherapy every 3 weeks: Paclitaxel 175mg/m2 IV over 3 hours on Day 4; Nedaplatin 80mg/m2 IV over 1 hours on Day 4; Endostar 3mg/day for 14 days continuous infusion from Day 1 to Day 14.

Primary Outcome Measures

Name	Time	Method
Progression free survival	From the date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Name	Time	Method
Overall survival	From the date of first drug administration until the date of death, assessed up to 36 months
Number of participants with AEs and SAEs as a measure of Safety	Each follow up vist, assessed up to 2 years	Each follow up visit, assessed up to 3 years. Date will be assessed at each study visiting using NCI CTCAE version 4.0.
Quality of life	Time from day 1 to date of death, assessed up to 3 years	Quality of life will be assessed at each study visit using EORTC QLQ-C30 and QLQ-OES18
Overall response rate (ORR)	From the date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China