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

Phase 2

Completed

• Conditions: Adenocarcinoma; Esophageal Cancer
• Interventions: Drug: Nimotuzumab; Drug: Cisplatin; Drug: Fluorouracil; Radiation: Radiotherapy

• Registration Number: NCT01249352
• Lead Sponsor: Eurofarma Laboratorios S.A.

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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2010-11-25
• Study First Submitted QC: 2010-11-26
• Study First Posted: 2010-11-29
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Status Verified: 2014-01
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
STANDARD CHEMORADIATION	Radiotherapy	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.
CHEMORADIATION + NIMOTUZUMAB	Radiotherapy	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.
STANDARD CHEMORADIATION	Nimotuzumab	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.
STANDARD CHEMORADIATION	Fluorouracil	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.
STANDARD CHEMORADIATION	Cisplatin	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.
CHEMORADIATION + NIMOTUZUMAB	Fluorouracil	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.
CHEMORADIATION + NIMOTUZUMAB	Cisplatin	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.
CHEMORADIATION + NIMOTUZUMAB	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.

Primary Outcome Measures

Name	Time	Method
Overall survival and assessment of the complete endoscopic response	2 years	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

Name	Time	Method
Complete clinical response rate	2 years	* 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.

Trial Locations

Locations (19)

Hospital Nossa Senhora da Conceição; 🇧🇷 Porto Alegre, RS, Brazil

Santa Casa de Misericórdia de BH; 🇧🇷 Belo Horizonte, MG, Brazil

Hospital Geral de Bonsucesso; 🇧🇷 Rio de Janeiro, RJ, Brazil

Hospital Universitário de Brasília; 🇧🇷 Brasília, DF, Brazil

Hospital da cidade de Passo Fundo; 🇧🇷 Passo Fundo, RS, Brazil

Centro Oncológico Mogi das Cruzes; 🇧🇷 Mogi das Cruzes, SP, Brazil

Centro de Estudos de Investigações Clíncas (CEIC); 🇧🇷 São Caetano do Sul, SP, Brazil

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil

Centro de Novos Tratamentos de Itajaí; 🇧🇷 Itajaí, SC, Brazil

Hospital São Paulo (UNIFESP); 🇧🇷 São Paulo, SP, Brazil

Hospital Evangélico do Cachoeiro do Itapemirim; 🇧🇷 Cachoeiro do Itapemirim, ES, Brazil

Hospital Erasto Gaetner; 🇧🇷 Curitiba, PR, Brazil

Instituto Nacional do Câncer (INCA); 🇧🇷 Rio de Janeiro, RJ, Brazil

Hospital Municipal São José; 🇧🇷 Joinville, SC, Brazil

Hospital Amaral Carvalho; 🇧🇷 Jau, SP, Brazil

Faculdade de Medicina do ABC / CEPHO; 🇧🇷 Santo André, SP, Brazil

Hospital Santa Marcelina; 🇧🇷 São Paulo, SP, Brazil

Hospital de Base; 🇧🇷 São José do Rio Preto, SP, Brazil

Instituto do Câncer do Estado de São Paulo; 🇧🇷 São Paulo, SP, Brazil