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

Esophageal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01249352
• Other study ID #: EF024-201
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 25, 2010
• Last updated: January 3, 2014
• Start date: January 2009
• Est. completion date: November 2013

Study information

• Verified date: January 2014
• Source: Eurofarma Laboratorios S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in ResearchBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• Nimotuzumab
200 mg, IV Weekly IV dose for up to 26 weeks.
• Cisplatin
75 mg/m2, IV dose on D1 of each chemotherapy cycle, for 4 cycles, always after nimotuzumab.
• 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

Locations

Country	Name	City	State
Brazil	Santa Casa de Misericórdia de BH	Belo Horizonte	MG
Brazil	Hospital Universitário de Brasília	Brasília	DF
Brazil	Hospital Evangélico do Cachoeiro do Itapemirim	Cachoeiro do Itapemirim	ES
Brazil	Hospital Erasto Gaetner	Curitiba	PR
Brazil	Centro de Novos Tratamentos de Itajaí	Itajaí	SC
Brazil	Hospital Amaral Carvalho	Jau	SP
Brazil	Hospital Municipal São José	Joinville	SC
Brazil	Centro Oncológico Mogi das Cruzes	Mogi das Cruzes	SP
Brazil	Hospital da cidade de Passo Fundo	Passo Fundo	RS
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceição	Porto Alegre	RS
Brazil	Hospital Geral de Bonsucesso	Rio de Janeiro	RJ
Brazil	Instituto Nacional do Câncer (INCA)	Rio de Janeiro	RJ
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 Santa Marcelina	São Paulo	SP
Brazil	Hospital São Paulo (UNIFESP)	São Paulo	SP
Brazil	Instituto do Câncer do Estado de São Paulo	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Eurofarma Laboratorios S.A.

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes