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A Study of Chemoradiation Associated With Nimotuzumab as the Treatment of Locally Advanced Esophageal Cancer (NICE)

Primary Purpose

Esophageal Cancer, Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Nimotuzumab
Cisplatin
Fluorouracil
Radiotherapy
Sponsored by
Eurofarma Laboratorios S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring Esophageal Cancer, Nimotuzumab, EF024, EF024-201

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Hospital Universitário de Brasília
  • Hospital Evangélico do Cachoeiro do Itapemirim
  • Santa Casa de Misericórdia de BH
  • Hospital Erasto Gaetner
  • Hospital Geral de Bonsucesso
  • Instituto Nacional do Câncer (INCA)
  • Hospital da cidade de Passo Fundo
  • Hospital de Clínicas de Porto Alegre
  • Hospital Nossa Senhora da Conceição
  • Centro de Novos Tratamentos de Itajaí
  • Hospital Municipal São José
  • Hospital Amaral Carvalho
  • Centro Oncológico Mogi das Cruzes
  • Faculdade de Medicina do ABC / CEPHO
  • Centro de Estudos de Investigações Clíncas (CEIC)
  • Hospital de Base
  • Hospital Santa Marcelina
  • Hospital São Paulo (UNIFESP)
  • Instituto do Câncer do Estado de São Paulo

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

STANDARD CHEMORADIATION

CHEMORADIATION + NIMOTUZUMAB

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
November 25, 2010
Last Updated
January 3, 2014
Sponsor
Eurofarma Laboratorios S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT01249352
Brief Title
A Study of Chemoradiation Associated With Nimotuzumab as the Treatment of Locally Advanced Esophageal Cancer
Acronym
NICE
Official Title
A Phase II, Randomized, Controlled, Open-Label Study Comparing Standard Chemoradiation Versus Chemoradiation Associated With Nimotuzumab as the Treatment of Locally Advanced Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eurofarma Laboratorios S.A.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer, Adenocarcinoma
Keywords
Esophageal Cancer, Nimotuzumab, EF024, EF024-201

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
STANDARD CHEMORADIATION
Arm Type
Active Comparator
Arm Description
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.
Arm Title
CHEMORADIATION + NIMOTUZUMAB
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nimotuzumab
Intervention Description
200 mg, IV Weekly IV dose for up to 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
75 mg/m2, IV dose on D1 of each chemotherapy cycle, for 4 cycles, always after nimotuzumab.
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Intervention Description
1,000 mg/m2, IV dose in a 24-hour continuous infusion, from D1 to D4, every chemotherapy cycle, for 4 cycles.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiotherapy 50.4 Gy, fractions of 1.8 Gy/day
Primary Outcome Measure Information:
Title
Overall survival and assessment of the complete endoscopic response
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Complete clinical response rate
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years; Histological prove of SCC or esophageal adenocarcinoma; T1N1M0, T2N1M0, T3N0M0, T4N0M0, T3N1M0, T4N1M0, qqTqqNM1a stage, according to the TNM system42; Life expectation above 6 months; 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); Performance status 0, 1, or 2, according to the Eastern Cooperative Oncology Group criteria44 (ECOG) (see Appendix C); Creatinine clearance ≥ 60 ml/min, according to the Cockcroft and Gault formula45 (see Appendix D); 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; Adequate calorie ingestion, at the investigator's discretion; He/she must have signed the informed consent form Exclusion Criteria: Previous or planned treatment of esophageal carcinoma with surgery, radiotherapy, chemotherapy, or antineoplastic biological therapy; Presence of active infection; Knowledge of the presence of HIV seropositivity; 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; Presence of a significant neurological or psychiatric disease, including dementia and seizures, as per the investigator's judgment; History of malignant neoplasm, except for adequately treated skin basal carcinoma or SCC, and cervical carcinoma in situ; Presence of peripheral neuropathy; Knowledge of the presence of hypersensitivity or allergy to drugs that will be administered in this protocol; History of severe allergic reaction; Pregnancy or lactation; Presence of aerodigestive fistula (trachea and/or bronchia); Evident presence of trachea and/or bronchia infiltration by the tumor; Presence of uncontrolled hypercalcaemia ≥ 2.9 mmol/L (or grade >1, according to the NCI-CTCAE, version 3.0).
Facility Information:
Facility Name
Hospital Universitário de Brasília
City
Brasília
State/Province
DF
Country
Brazil
Facility Name
Hospital Evangélico do Cachoeiro do Itapemirim
City
Cachoeiro do Itapemirim
State/Province
ES
Country
Brazil
Facility Name
Santa Casa de Misericórdia de BH
City
Belo Horizonte
State/Province
MG
Country
Brazil
Facility Name
Hospital Erasto Gaetner
City
Curitiba
State/Province
PR
Country
Brazil
Facility Name
Hospital Geral de Bonsucesso
City
Rio de Janeiro
State/Province
RJ
Country
Brazil
Facility Name
Instituto Nacional do Câncer (INCA)
City
Rio de Janeiro
State/Province
RJ
Country
Brazil
Facility Name
Hospital da cidade de Passo Fundo
City
Passo Fundo
State/Province
RS
Country
Brazil
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
RS
Country
Brazil
Facility Name
Hospital Nossa Senhora da Conceição
City
Porto Alegre
State/Province
RS
Country
Brazil
Facility Name
Centro de Novos Tratamentos de Itajaí
City
Itajaí
State/Province
SC
Country
Brazil
Facility Name
Hospital Municipal São José
City
Joinville
State/Province
SC
Country
Brazil
Facility Name
Hospital Amaral Carvalho
City
Jau
State/Province
SP
Country
Brazil
Facility Name
Centro Oncológico Mogi das Cruzes
City
Mogi das Cruzes
State/Province
SP
Country
Brazil
Facility Name
Faculdade de Medicina do ABC / CEPHO
City
Santo André
State/Province
SP
Country
Brazil
Facility Name
Centro de Estudos de Investigações Clíncas (CEIC)
City
São Caetano do Sul
State/Province
SP
Country
Brazil
Facility Name
Hospital de Base
City
São José do Rio Preto
State/Province
SP
Country
Brazil
Facility Name
Hospital Santa Marcelina
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Hospital São Paulo (UNIFESP)
City
São Paulo
State/Province
SP
Country
Brazil
Facility Name
Instituto do Câncer do Estado de São Paulo
City
São Paulo
State/Province
SP
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
29179134
Citation
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.
Results Reference
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A Study of Chemoradiation Associated With Nimotuzumab as the Treatment of Locally Advanced Esophageal Cancer

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