Cetuximab/Paclitaxel/Cisplatin Concurrent Chemoradiotherapy Followed by Esophagectomy for Loco-regional Esophageal Cancer

A Phase II Study of Combining Cetuximab Plus Twice Weekly Paclitaxel/Cisplatin Concurrent Chemoradiotherapy (TP-CCRT) Followed With or Without Esophagectomy for Loco-regional Esophageal Squamous Cell Carcinoma (ESCC)

We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy (TP-CCRT) as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Unknown
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: Paclitaxel; Drug: Cisplatin; Radiation: Radiotherapy

Detailed Description

We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chih-Hung Hsu, M.D., Ph.D.; Phone Number: 67680 886-2-23123456; Email: chihhunghsu@ntu.edu.tw
    • Principal Investigator: Chih-Hung Hsu, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pathologically proven squamous cell carcinoma of esophagus.

2. Loco-regional diseases, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (6th edition) in 2002, fulfilling one of the following criteria:

   A. T3, N0, M0; B. T1-3, N1, M0; C. T1-3 or N0-1, M1a will be eligible provided the lesions could be covered by appropriate radiation fields.

3. Age ≥ 18 years old.
4. Performance status ECOG 0~2.

5. Adequate bone marrow reserves, defined as:

   A. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; B. platelets ≥ 100,000/µl.

6. Adequate liver function reserves, defined as:

   A. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); B. serum total bilirubin ≤ 1.5 x upper limit of normal (ULN).

7. Adequate renal function: Creatinine ≤1.5 mg/dl
8. Written informed consent.

Exclusion Criteria:

1. Invasion to surrounding organ (T4 disease).
2. Distant metastasis, except M1a disease listed in the inclusion criteria 2-C.
3. Adenocarcinoma of gastroesophageal (GE) junction.
4. Prior thoracic irradiation.
5. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer.

6. Prior malignancy, except for the following:

   A. adequately treated basal cell or squamous cell skin cancer; B. in-situ cervical cancer; C. Note: previously treated aerodigestive squamous cell carcinoma is not allowed.

7. Significant co-morbid disease, which prohibit the conduction of chemotherapy, concurrent chemoradiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders.
8. Estimated life expectancy less than 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Targeted therapy; Concurrent chemoradiotherapy with cetuximab, paclitaxel, and cisplatin followed by, if feasible, esophagectomy

Drug: Cetuximab; Cetuximab: loading dose 400 mg/m2, 2h- IVF, 3~ 5 days prior to starting CCRT (on week-1); followed by 250 mg/m2/ week, 1h- IVF, for 4 weeks (i.e., week 1 to week 4. during CCRT).; Other Names: Erbitux; Drug: Paclitaxel; T: Paclitaxel 35 mg/m2, 1h IVF, on day 1 and day 4 of each week, week1 to week4 during CCRT.; Drug: Cisplatin; P: Cisplatin 15 mg/m2, 1 h IVF, on day 2 and day 5 of each week, week1 to week4 during CCRT.; Radiation: Radiotherapy; Radiotherapy: (three-dimensional conformal radiotherapy or intensity modulated radiotherapy) 200 cGy/fraction, once daily, 5 days a week, to a total dose of 4000 cGy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the clinical response rate in patients with loco-regional esophageal squamous cell carcinoma treated with cetuximab combined with twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy (C-TP-CCRT, 40 Gy).	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Pathologic complete response (pCR).	2 years
Disease-free survival.	2 years
Safety and toxicity of cetuximab combined with twice weekly TP-CCRT, followed by surgery.	2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Yung-Chie Lee, M.D., National Taiwan University Hospital

Publications and helpful links

General Publications

• Guo JC, Huang TC, Lin CC, Hsieh MS, Chang CH, Huang PM, Lee JM, Hsu FM, Chia-Hsien Cheng J, Wang HP, Yeh KH, Cheng AL, Hsu CH. Postchemoradiotherapy Pathologic Stage Classified by the American Joint Committee on the Cancer Staging System Predicts Prognosis of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma. J Thorac Oncol. 2015 Oct;10(10):1481-9. doi: 10.1097/JTO.0000000000000651.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: December 16, 2009
• First Submitted That Met QC Criteria: December 16, 2009
• First Posted (Estimate): December 17, 2009

Study Record Updates

• Last Update Posted (Estimate): December 17, 2009
• Last Update Submitted That Met QC Criteria: December 16, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Cetuximab; Paclitaxel; Esophageal cancer; Chemoradiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Cetuximab
• Other Study ID Numbers: 200803088M