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

• ClinicalTrials.gov Identifier: NCT01249352
• Recruitment Status: Completed
• First Posted: November 29, 2010
• Last Update Posted: January 6, 2014
• Sponsor: Eurofarma Laboratorios S.A.
• Information provided by: Eurofarma Laboratorios S.A.

Tracking Information

• First Submitted Date: November 25, 2010
• First Posted Date: November 29, 2010
• Last Update Posted Date: January 6, 2014
• Study Start Date: January 2009
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2010)

Overall survival and assessment of the complete endoscopic response [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 26, 2010)

Complete clinical response rate [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Esophageal Cancer
• Adenocarcinoma

Intervention

• 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

Study Arms

• 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.

  Interventions:

  • Drug: Nimotuzumab
  • Drug: Cisplatin
  • Drug: Fluorouracil
  • Radiation: Radiotherapy
• 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.

  Interventions:

  • Drug: Nimotuzumab
  • Drug: Cisplatin
  • Drug: Fluorouracil
  • Radiation: Radiotherapy

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 26, 2010): 104
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2013
• Actual Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil

Administrative Information

• NCT Number: NCT01249352
• Other Study ID Numbers: EF024-201
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Gilberto Castro / Dr. Rafael Schimmerling, HCFMUSP
• Original Responsible Party: Same as current
• Current Study Sponsor: Eurofarma Laboratorios S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Eurofarma Laboratorios S.A.
• Verification Date: January 2014