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

This study has been completed.
Sponsor:
Information provided by:
Eurofarma Laboratorios S.A.
ClinicalTrials.gov Identifier:
NCT01249352
First received: November 25, 2010
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Adenocarcinoma
Drug: Nimotuzumab
Drug: Cisplatin
Drug: Fluorouracil
Radiation: Radiotherapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eurofarma Laboratorios S.A.:

Primary Outcome Measures:
  • Overall survival and assessment of the complete endoscopic response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 Frame: 2 years ] [ Designated as safety issue: Yes ]
    • 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.


Enrollment: 104
Study Start Date: January 2009
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249352

Locations
Brazil
Hospital Universitário de Brasília
Brasília, DF, Brazil
Hospital Evangélico do Cachoeiro do Itapemirim
Cachoeiro do Itapemirim, ES, Brazil
Santa Casa de Misericórdia de BH
Belo Horizonte, MG, Brazil
Hospital Erasto Gaetner
Curitiba, PR, Brazil
Instituto Nacional do Câncer (INCA)
Rio de Janeiro, RJ, Brazil
Hospital Geral de Bonsucesso
Rio de Janeiro, RJ, Brazil
Hospital da cidade de Passo Fundo
Passo Fundo, RS, Brazil
Hospital Nossa Senhora da Conceição
Porto Alegre, RS, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, RS, Brazil
Centro de Novos Tratamentos de Itajaí
Itajaí, SC, Brazil
Hospital Municipal São José
Joinville, SC, Brazil
Hospital Amaral Carvalho
Jau, SP, Brazil
Centro Oncológico Mogi das Cruzes
Mogi das Cruzes, SP, Brazil
Faculdade de Medicina do ABC / CEPHO
Santo André, SP, Brazil
Centro de Estudos de Investigações Clíncas (CEIC)
São Caetano do Sul, SP, Brazil
Hospital de Base
São José do Rio Preto, SP, Brazil
Hospital São Paulo (UNIFESP)
São Paulo, SP, Brazil
Instituto do Câncer do Estado de São Paulo
São Paulo, SP, Brazil
Hospital Santa Marcelina
São Paulo, SP, Brazil
Sponsors and Collaborators
Eurofarma Laboratorios S.A.
  More Information

No publications provided

Responsible Party: Dr. Gilberto Castro / Dr. Rafael Schimmerling, HCFMUSP
ClinicalTrials.gov Identifier: NCT01249352     History of Changes
Other Study ID Numbers: EF024-201
Study First Received: November 25, 2010
Last Updated: January 3, 2014
Health Authority: Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency

Keywords provided by Eurofarma Laboratorios S.A.:
Esophageal Cancer
Nimotuzumab
EF024
EF024-201

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014