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

A Phase II, Randomized, Controlled, Open-Label Study Comparing Standard Chemoradiation Versus Chemoradiation Associated with Nimotuzumab As the Treatment of Locally Advanced Esophageal Cancer

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.

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.

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).