A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma

NCT02409186 | Unknown Phase 3 DMC

• 1 other identifier: NXCEL1311
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 14

Brief Summary

Esophageal cancer is the sixth leading cause of cancer death in worldwide. Over the past 2 decades, well-designed clinical trials have documented the clinical benefits of combination of chemotherapy and radiation for localized esophageal cancer, either as primary therapy or in neoadjuvant setting. Paclitaxel, a radiation sensitizer, has important single-agent activity in esophageal cancer. Paclitaxel-based chemoradiation has been the framework for the recent Radiation Therapy Oncology Group (RTOG) trials of nonoperative management of esophageal cancer. Accumulating clinical evidence suggests that Epidermal Growth Factor Receptor (EGFR) represents a viable target in the treatment of esophageal cancer. EGFR expression is associated with poor prognosis. Nimotuzumab binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of Epidermal Growth Factor (EGF) and other ligands, such as Transforming Growth Factor-α (TGF-α). Preclinical models have suggested synergy between nimotuzumab, paclitaxel, cisplatin and radiation. For our phase II study in locally advanced esophageal squamous cell carcinoma (ESCC), the combination of cetuximab and chemoradiotherapy has demonstrated both response and survival benefits. Myara et al reported that nimotuzumab plus concurrent chemoradiation therapy (CCRT) was safe and provided statistically significant objective response (47.8%) and disease control rate (60.9%) in nonresectable ESCC. With all these, the investigators plan to study phase III trial.

Conditions

Prosthesis Survival

Outcome Measures

Primary Outcomes (1)

• Over Survival

  up to 5 years

Study Arms (2)

Nimotuzumab plus chemoradiotherapy

ACTIVE COMPARATOR

Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7

Drug: Nimotuzumab; Radiation: radiotherapy; Drug: chemoradiotherapy Paclitaxel; Drug: chemoradiotherapy Cisplatin

placebo plus chemoradiotherapy

PLACEBO COMPARATOR

placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7

Radiation: radiotherapy; Drug: chemoradiotherapy Paclitaxel; Drug: chemoradiotherapy Cisplatin; Other: placebo

Interventions

Nimotuzumab DRUG

400mg/w，d1, week 1-7

Also known as: Taixinsheng

Nimotuzumab plus chemoradiotherapy

radiotherapy RADIATION

Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7

Nimotuzumab plus chemoradiotherapy; placebo plus chemoradiotherapy

chemoradiotherapy Paclitaxel DRUG

45 mg/m2, d1, week 1-7

Also known as: Paclitaxel

Nimotuzumab plus chemoradiotherapy; placebo plus chemoradiotherapy

chemoradiotherapy Cisplatin DRUG

20 mg/m2, d1, week 1-7

Also known as: Cisplatin

Nimotuzumab plus chemoradiotherapy; placebo plus chemoradiotherapy

placebo OTHER

400mg/w，d1, week 1-7

placebo plus chemoradiotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to study entry
• age：18-70 years
• Histopathology confirmed primary esophageal squamous cell carcinoma, meet one of the following criteria (AJCC Staging System，2009，Seventh Edition):Cervical esophageal carcinoma(stage II-III);upper thoracic esophageal cancer or chest esophageal cancer that is unsuitable or refuse surgery (stage II-III)
• The existence of measurable lesions (according to Response Evaluation Criteria in Solid Tumors 1.1)
• Eastern Cooperative Oncology Group（ECOG）Performance status of 0-1
• Possible semi-liquid diet
• If there is a risk of pregnancy, male and female subjects must be effective contraception during treatment
• Normal bone marrow reserve: neutrophil (ANC) count≥1500/mm3,platelet count≥100,000 /mm3, hemoglobin≥5.6mmol/L(9g/dL)
• Normal renal function: serum creatinine≤1.5mg/dl and/or calculated creatinine clearance≥ 60ml/min
• Normal hepatic function: bilirubin level≤1.5×ULN, alanine aminotransferase aspartate transaminase（ASAT）\& ALST≤1.5×ULN
• Subjects tumor tissue available for the relevant biomarker detection

You may not qualify if:

• Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
• Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor（VEGF）therapy or EGFR-pathway targeting therapy not indicated in this study protocol
• Multiple primary carcinomas of the esophagus
• Pregnancy (confirmed by urine β-HCG) or lactation period
• Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
• There are obvious esophageal ulcers, chest and back more than moderate pain, symptoms of esophageal perforation
• Unable to comprehend the study requirements or who are not likely to comply with the study requirements
• Patients with distant metastasis
• Patients with other malignant disease, except for curable non-melanoma skin cancer, cervical carcinoma in situ or malignant disease cure for≥5 years
• Known grade 3 or 4 allergic reaction to any of the study treatment
• Peripheral neuropathy \> grade 1
• Participation in another clinical study within the past 30 days
• Significant disease which, in the investigator's opinion, would exclude the patient from the study

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (14)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, 515041, China

NOT YET RECRUITING

The Guangxi Zhuang Autonomous Region Cancer Hospita

Nanning, Guangxi, 530021, China

NOT YET RECRUITING

Affiliated Hospital of Zunyi Medical College

Zunyi, Guizhou, 563099, China

NOT YET RECRUITING

Fourth Hospital of Hebei Medical University Tumor

Shijiazhuang, Hebei, 50011, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, 212013, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 310022, China

RECRUITING

Shandong Cancer Hospital and Institute

Jinan, Shandong, 250117, China

RECRUITING

Renji Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

NOT YET RECRUITING

The First Hospital of Zhejiang Province

Hangzhou, Zhejiang, 310003, China

NOT YET RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

Related Publications (1)

• Meng X, Zheng A, Wang J, Wu X, Li G, Zhu J, Ma H, Zhu X, Shi A, Dai C, Yan S, Wang B, Qu Z, Han C, Sun X, Ye M, Fan R, Huerxidan N, Wang X, Yu J. Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial. Br J Cancer. 2023 Nov;129(11):1787-1792. doi: 10.1038/s41416-023-02388-7. Epub 2023 Oct 20.

  PMID: 37864049 DERIVED

MeSH Terms

Conditions

Prosthesis Failure

Interventions

nimotuzumab; Radiotherapy; Paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jinming Yu, Ph.D, M.D

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

• Xue Meng, Ph.D, M.D

  Shandong Cancer Hospital and Institute

  STUDY DIRECTOR

Central Study Contacts

Jinming Yu, Ph.D, M.D

CONTACT

13806406293; jn7984729@public.jn.sd.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: April 6, 2015
• Study Start: March 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2021
• Last Updated: April 21, 2016

Record last verified: 2016-04

Locations

CN (14)