Clinical trial NCT01249352: A Study of Chemoradiation Associated with Nimotuzumab As the Treatment of Locally Advanced Esophageal Cancer
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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Esophageal Cancer
Adenocarcinoma
Keywords: Esophageal Cancer
Nimotuzumab
EF024
EF024-201
Lead sponsor: Eurofarma Laboratorios S.A.
Sponsor class: INDUSTRY
First posted: 2010-11-29
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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).

Primary outcomes:
measure: Overall survival and assessment of the complete endoscopic response
timeFrame: 2 years
Secondary outcomes:
measure: Complete clinical response rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Brasília
country: Brazil
facility: Hospital Universitário de Brasília
state: DF
city: Cachoeiro do Itapemirim
country: Brazil
facility: Hospital Evangélico do Cachoeiro do Itapemirim
state: ES
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericórdia de BH
state: MG
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaetner
state: PR
city: Rio de Janeiro
country: Brazil
facility: Hospital Geral de Bonsucesso
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Câncer (INCA)
state: RJ
city: Passo Fundo
country: Brazil
facility: Hospital da cidade de Passo Fundo
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição
state: RS
city: Itajaí
country: Brazil
facility: Centro de Novos Tratamentos de Itajaí
state: SC
city: Joinville
country: Brazil
facility: Hospital Municipal São José
state: SC
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Mogi das Cruzes
country: Brazil
facility: Centro Oncológico Mogi das Cruzes
state: SP
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC / CEPHO
state: SP
city: São Caetano do Sul
country: Brazil
facility: Centro de Estudos de Investigações Clíncas (CEIC)
state: SP
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base
state: SP
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: SP
city: São Paulo
country: Brazil
facility: Hospital São Paulo (UNIFESP)
state: SP
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo
state: SP
Study officials:
References:
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.