Definitive Radiochemotherapy Plus/Minus Cetuximab in Unresectable Locally Advanced Esophageal Cancer

NCT01787006 | Completed Phase 2 Results DMC

• 2 other identifiers: LEOPARD II2010-023427-18
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Esophageal cancer is a highly aggressive tumor. Treatment options are various and range from chemotherapy to radiotherapy and several surgical techniques. Nevertheless, the overall survival rates for this disease remain poor. During the last years the combination of cetuximab with standard chemotherapy or radiotherapy has mainly be investigated in clinical trials focusing on colorectal and/or head and neck cancer. The results obtained from theses studies were very encouraging and led to the initiation of active clinical research in esophageal cancer patients with antibody inhibition of the epidermal growth factor receptor (EGFR). The first data in this indication are encouraging showing that cetuximab can safely be added to chemoradiation for esophageal cancer patients with first hints of efficacy. Based on the experiences with cetuximab in colorectal cancer and in combination with radiotherapy in head and neck cancer, the aim of the present study is to evaluate the feasibility of a combined treatment of cetuximab with continuous infusional 5-FU, cisplatin and radiotherapy in patients with esophageal cancer and to assess if the overall survival rates can be increased by addition of an EGFR-targeted therapy.

Conditions

Esophageal Cancer

Keywords

non resectable; locally advanced; Cetuximab; radiation

Outcome Measures

Primary Outcomes (1)

• Rate of Participants Who Were Alive at 2 Years

  Overall Survival (OS) was defined as freedom from death of any cause. Time to death was calculated from the day of randomization, and the patients were followed for a maximum of 24 months (2 years).

  2 years

Secondary Outcomes (10)

• Rate of Participants Who Were Alive at 1 Year

  1 year

• Rate of Participants Who Were Alive Without Progression of Disease at 1 Year

  1 year

• Rate of Participants Who Were Alive Without Progression of Disease at 2 Years

  2 years

• Number of Participants Experiencing at Least One Grade >=3 Toxicity

  up to 2 years

• Rate of Participants Who Were Alive Without Distant Metastases at 1 Year

  1 year

Study Arms (2)

Cetuximab, Cisplatin, 5-FU, Radiotherapy

EXPERIMENTAL

Cetuximab: Initial doses 400mg/m2 (day 1), followed by weekly doses of 250mg/m2 for 14 weeks in total, IV 5-fluorouracil (5-FU): 1000mg/m2 per day as continuous infusion on day 8-11 and 36-39, 750mg/m2/day as continuous infusion on day 71-74 and 99-102 Cisplatin 20mg/m2/day as intravenous bolus over 60 min on day 1-4 of every cycle (day 8-11, 36-39, 71-74 and 99-102) radiotherapy: 59.4 Gy (33 fractions of 1.8 Gy) over 6.5-7 weeks (5 x 1.8 Gy per week)on primary tumor. 50.4 Gy on locoregional lymphnodes. If resectability is reached after 4-4.5 weeks (36-41.4 Gy) the radiotherapy stops after 45 Gy and the patient undergoes surgery.

Drug: Cetuximab; Drug: Cisplatin, 5-FU; Radiation: Radiotherapy

Cisplatin, 5-FU, Radiotherapy

ACTIVE COMPARATOR

5-FU: 1000mg/m2 per day as continuous infusion on day 1-4 and 29-32, 750mg/m2/day as continuous infusion on day 64-67 and 92-95 Cisplatin 20mg/m2/day as intravenous bolus over 60 min on day 1-4 of every cycle (day 1-4, 29-32, 64-67 and 92-95) radiotherapy: 59.4 Gy (33 fractions of 1.8 Gy) over 6.5-7 weeks (5 x 1.8 Gy per week)on primary tumor. 50.4 Gy on locoregional lymphnodes. If resectability is reached after 4-4.5 weeks (36-41.4 Gy) the radiotherapy stops after 45 Gy and the patient undergoes surgery.

Drug: Cisplatin, 5-FU; Radiation: Radiotherapy

Interventions

Cetuximab DRUG

Initial doses 400mg/m2 (day 1), followed by weekly doses of 250mg/m2 for 14 weeks in total

Also known as: Erbitux

Cetuximab, Cisplatin, 5-FU, Radiotherapy

Cisplatin, 5-FU DRUG

5-FU: 1000mg/m2 per day as continuous infusion on day 1-4 of cycle 1 and 2, 750mg/m2/day as continuous infusion on day 1-4 of cycle 3 and 4 Cisplatin 20mg/m2/day as intravenous bolus over 60 min on day 1-4 of every cycle

Also known as: CDDP, 5-fluorouracil

Cetuximab, Cisplatin, 5-FU, Radiotherapy; Cisplatin, 5-FU, Radiotherapy

Radiotherapy RADIATION

59.4 Gy (33 fractions of 1.8 Gy) over 6.5-7 weeks (5 x 1.8 Gy per week)on primary tumor. 50.4 Gy on locoregional lymphnodes. If resectability is reached after 4-4.5 weeks (36-41.4 Gy) the radiotherapy stops after 45 Gy and the patient undergoes surgery.

Also known as: Irradiation

Cetuximab, Cisplatin, 5-FU, Radiotherapy; Cisplatin, 5-FU, Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dated and signed written informed consent
• Male or female patients between 18 years and 75 years; patients \> 75 years if their karnofsky performance status is ≥ 80.
• Histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus which is not curatively resectable. Resectability has to be defined by a surgeon before radiochemotherapy. The tumor is considered unresectable due to T-stage, N-stage, performance status, nutritional status, co-morbidity (pulmonal function, other), tumor location upper third or other reasons
• Karnofsky Performance Status ≥ 70
• Women of child-bearing potential must have a negative pregnancy test
• Adequate cardial-, pulmonal- and ear function
• Adequate bone marrow function:
• leukocytes ≥ 3.0 x 10\^9/L
• neutrophiles ≥ 1.5 x 10\^9/L
• thrombocytes ≥ 100 x 10\^9/L
• hemoglobin ≥ 10.0 g/dl
• Adequate liver function:
• bilirubin ≤ 2.0 mg/dl
• transaminases (serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-GT) ≤ 3 x upper limit of normal (ULN)
• Adequate kidney function:

You may not qualify if:

• distant metastasis
• previous treatment of esophageal cancer
• previous therapy with monoclonal antibodies and / or EGFR-targeted therapy
• previous second malignancies with exception of a history of a previous curatively treated basal cell carcinoma of the skin or pre-invasive cervix carcinoma
• serious concomitant disease or medical condition
• lung function: forced expiratory volume in one second (FEV1)) \< 1.1
• clinically relevant coronary artery diseases or known myocardial infarction within the last 12 months or ventricular ejection fraction (LVEF) below normal
• every active dermatological condition \> grade 1
• contraindications to receive cisplatin, 5-FU or cetuximab
• concurrent treatment with other experimental drugs or participation in another clinical trial within 30 days before study start
• patient pregnant or breast feeding
• known drug abuse, medication abuse, alcohol abuse
• social situations limiting the compliance with the study requirements

Sponsors & Collaborators

• University Hospital Schleswig-Holstein: lead

Study Sites (1)

Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik für Strahlentherapie

Lübeck, 23538, Germany

Location

Related Publications (1)

• Rades D, Bartscht T, Hunold P, Schmidberger H, Konig L, Debus J, Belka C, Homann N, Spillner P, Petersen C, Kuhnt T, Fietkau R, Ridwelski K, Karcher-Kilian K, Kranich A, Mannikko S, Schild SE, Maderer A, Moehler M. Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2). Strahlenther Onkol. 2020 Sep;196(9):795-804. doi: 10.1007/s00066-020-01646-4. Epub 2020 Jun 12.

  PMID: 32533228 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Cetuximab; Cisplatin; Fluorouracil; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Prof. Dr. med. Dirk Rades
• Organization: Department of Radiation Oncology, University of Lübeck, Germany

dirk.rades@uksh.de

0049 451 500

Study Officials

• Dirk Rades, Prof. Dr.

  Universität zu Lübeck, Klinik für Strahlentherapie

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr. med.

Study Record Dates

• First Submitted: February 5, 2013
• First Posted: February 8, 2013
• Study Start: September 1, 2011
• Primary Completion: September 6, 2018
• Study Completion: September 6, 2018
• Last Updated: March 10, 2020
• Results First Posted: March 10, 2020

Record last verified: 2020-03

Locations

DE (1)