A Study of Chemoradiation Associated with Nimotuzumab As the Treatment of Locally Advanced Esophageal Cancer (NICE)

A Phase II, Randomized, Controlled, Open-Label Study Comparing Standard Chemoradiation Versus Chemoradiation Associated with Nimotuzumab As the Treatment of Locally Advanced Esophageal Cancer

The primary objective of this study is to assess the efficacy of nimotuzumab in combination with chemotherapy and radiotherapy for the treatment of locally advanced esophageal cancer, comparing it to that of the conventional treatment with radiation and chemotherapy.

The secondary objective of this study is to assess the health-related quality of life for the nimotuzumab in combination with chemotherapy and radiotherapy regimen, compared to the standard chemoradiation regimen in the treatment of inoperable locally advanced esophageal cancer.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma; Esophageal Cancer
• Intervention / Treatment: Drug: Nimotuzumab; Drug: Cisplatin; Drug: Fluorouracil; Radiation: Radiotherapy

Detailed Description

This will be a phase II, randomized, controlled, open-label, multicenter, and two-arm study. The study will be conducted in Brazil and has the purpose of determining the activity and safety of nimotuzumab in terms of overall survival, TTP, clinical and endoscopic response rates, resectability rate, toxicity profile, and quality of life. All participating patients will sign a consent form before they undergo any study-related procedure. The eligible patients will have locally advanced esophageal cancer, and they will be randomized to one of two treatment groups. Randomization will be centrally coordinated by the sponsor and performed by means of the electronic CRF itself.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • DF
    • Brasília, DF, Brazil
      • Hospital Universitario de Brasilia
  • ES
    • Cachoeiro do Itapemirim, ES, Brazil
      • Hospital Evangélico do Cachoeiro do Itapemirim
  • MG
    • Belo Horizonte, MG, Brazil
      • Santa Casa de Misericórdia de BH
  • PR
    • Curitiba, PR, Brazil
      • Hospital Erasto Gaetner
  • RJ
    • Rio de Janeiro, RJ, Brazil
      • Hospital Geral de Bonsucesso
    • Rio de Janeiro, RJ, Brazil
      • Instituto Nacional Do Cancer (INCA)
  • RS
    • Passo Fundo, RS, Brazil
      • Hospital da cidade de Passo Fundo
    • Porto Alegre, RS, Brazil
      • Hospital de Clínicas de Porto Alegre
    • Porto Alegre, RS, Brazil
      • Hospital Nossa Senhora Da Conceição
  • SC
    • Itajaí, SC, Brazil
      • Centro de Novos Tratamentos de Itajaí
    • Joinville, SC, Brazil
      • Hospital Municipal São José
  • SP
    • Jau, SP, Brazil
      • Hospital Amaral Carvalho
    • Mogi das Cruzes, SP, Brazil
      • Centro Oncologico Mogi das Cruzes
    • Santo André, SP, Brazil
      • Faculdade de Medicina do ABC / CEPHO
    • São Caetano do Sul, SP, Brazil
      • Centro de Estudos de Investigações Clíncas (CEIC)
    • São José do Rio Preto, SP, Brazil
      • Hospital de Base
    • São Paulo, SP, Brazil
      • Hospital Santa Marcelina
    • São Paulo, SP, Brazil
      • Hospital São Paulo (UNIFESP)
    • São Paulo, SP, Brazil
      • Instituto do Cancer do Estado de Sao Paulo

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years;
2. Histological prove of SCC or esophageal adenocarcinoma;
3. T1N1M0, T2N1M0, T3N0M0, T4N0M0, T3N1M0, T4N1M0, qqTqqNM1a stage, according to the TNM system42;
4. Life expectation above 6 months;
5. Inoperable superior, medial, or distal third esophageal cancer, including GE junction tumors, defined as type I and II tumors in the Siewert classification43 (see Appendix B);
6. Performance status 0, 1, or 2, according to the Eastern Cooperative Oncology Group criteria44 (ECOG) (see Appendix C);
7. Creatinine clearance ≥ 60 ml/min, according to the Cockcroft and Gault formula45 (see Appendix D);

8. Adequate body functions, indicated by

   • Creatinine clearance ≥ 60 ml/min;
   • Bilirubin, transaminase, alkaline phosphatase, and gamma-GT < 1,5 x the upper limit of normal;
   • leucocytes ≥ 3000/μl;
   • granulocytes ≥ 1500/ μl;
   • hemoglobin ≥ 9 g/dl;
   • platelets ≥ 80000/ μl;
9. Adequate calorie ingestion, at the investigator's discretion;
10. He/she must have signed the informed consent form

Exclusion Criteria:

1. Previous or planned treatment of esophageal carcinoma with surgery, radiotherapy, chemotherapy, or antineoplastic biological therapy;
2. Presence of active infection;
3. Knowledge of the presence of HIV seropositivity;
4. Presence of severe comorbidities that, in the investigator's opinion, will put the patient at a significantly higher risk or will damage the protocol compliance;
5. Presence of a significant neurological or psychiatric disease, including dementia and seizures, as per the investigator's judgment;
6. History of malignant neoplasm, except for adequately treated skin basal carcinoma or SCC, and cervical carcinoma in situ;
7. Presence of peripheral neuropathy;
8. Knowledge of the presence of hypersensitivity or allergy to drugs that will be administered in this protocol;
9. History of severe allergic reaction;
10. Pregnancy or lactation;
11. Presence of aerodigestive fistula (trachea and/or bronchia);
12. Evident presence of trachea and/or bronchia infiltration by the tumor;
13. Presence of uncontrolled hypercalcaemia ≥ 2.9 mmol/L (or grade >1, according to the NCI-CTCAE, version 3.0).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: STANDARD CHEMORADIATION; Cisplatin 75 mg/m2, IV IV doses on D1 of each chemotherapy cycle, for 4 cycles Fluorouracil 1000 mg/m2, IV IV doses in a 24-hour continuous infusion, from D1 to D4 of each chemotherapy cycle, for 4 cycles. Radiotherapy 50.4 Gy, fractions of 1.8 Gy/day Equivalent to 28 fractions for 5 and a half weeks.	Drug: Nimotuzumab; 200 mg, IV Weekly IV dose for up to 26 weeks.; Drug: Cisplatin; 75 mg/m2, IV dose on D1 of each chemotherapy cycle, for 4 cycles, always after nimotuzumab.; Drug: Fluorouracil; 1,000 mg/m2, IV dose in a 24-hour continuous infusion, from D1 to D4, every chemotherapy cycle, for 4 cycles.; Radiation: Radiotherapy; Radiotherapy 50.4 Gy, fractions of 1.8 Gy/day
Experimental: CHEMORADIATION + NIMOTUZUMAB; Nimotuzumab 200 mg, IV weekly IV doses for up to 26 weeks. Cisplatin 75 mg/m2, IV IV dose on D1 of each chemotherapy cycle, for 4 cycles, always after nimotuzumab. Fluorouracil 1000 mg/m2, IV IV dose in a 24-hour continuous infusion, from D1 to D4 of each chemotherapy cycle, for 4 cycles. Radiotherapy 50.4 Gy, fractions of 1.8 Gy/day Equivalent to 28 fractions for 5 and a half weeks.	Drug: Nimotuzumab; 200 mg, IV Weekly IV dose for up to 26 weeks.; Drug: Cisplatin; 75 mg/m2, IV dose on D1 of each chemotherapy cycle, for 4 cycles, always after nimotuzumab.; Drug: Fluorouracil; 1,000 mg/m2, IV dose in a 24-hour continuous infusion, from D1 to D4, every chemotherapy cycle, for 4 cycles.; Radiation: Radiotherapy; Radiotherapy 50.4 Gy, fractions of 1.8 Gy/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival and assessment of the complete endoscopic response	The primary endpoint of this study is the overall survival at the end of Phase II. At the end of Phase II, the assessment of the complete endoscopic response, and the regimen safety will be used to decide if the study will continue to Phase III.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clinical response rate	Time to tumor progression (TTP);; Complete clinical response rate, defined as the proportion of patients with absence of visible disease in the high endoscopy and in the chest and abdomen computerized tomography, in the population assessable for response;; Complete endoscopic response rate, defined as the absence of visible disease in the high endoscopy;; Resectability rate;; Safety:; Quality of life, according to the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire;; Relationship between efficacy and safety and the tumor characteristics.	2 years

Collaborators and Investigators

• Sponsor: Eurofarma Laboratorios S.A.

Publications and helpful links

General Publications

• de Castro Junior G, Segalla JG, de Azevedo SJ, Andrade CJ, Grabarz D, de Araujo Lima Franca B, Del Giglio A, Lazaretti NS, Alvares MN, Pedrini JL, Kussumoto C, de Matos Neto JN, Forones NM, Fernandes Junior HJ, Borges G, Girotto G, da Silva IDCG, Maluf-Filho F, Skare NG. A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial. Eur J Cancer. 2018 Jan;88:21-30. doi: 10.1016/j.ejca.2017.10.005. Epub 2017 Nov 24.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 25, 2010
• First Submitted That Met QC Criteria: November 26, 2010
• First Posted (Estimated): November 29, 2010

Study Record Updates

• Last Update Posted (Actual): March 31, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Esophageal Cancer; Nimotuzumab; EF024; EF024-201
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Fluorouracil; Nimotuzumab
• Other Study ID Numbers: EF024-201