Phase 2
N=74
Definitive Radiochemotherapy Plus/Minus Cetuximab in Unresectable Locally Advanced Esophageal Cancer
Esophageal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01787006 ↗Enrolled (actual)
74
Serious AEs
66.2%
Results posted
Mar 2020
Primary outcome: Primary: Rate of Participants Who Were Alive at 2 Years — 71; 53 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cetuximab (Drug); Cisplatin, 5-FU (Drug); Radiotherapy (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University Hospital Schleswig-Holstein
- Primary completion
- Sep 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Participants Who Were Alive at 2 Years |
71; 53 | — |
| SECONDARY Rate of Participants Who Were Alive at 1 Year |
74; 70 | — |
| SECONDARY Rate of Participants Who Were Alive Without Progression of Disease at 1 Year |
64; 58 | — |
| SECONDARY Rate of Participants Who Were Alive Without Progression of Disease at 2 Years |
56; 44 | — |
| SECONDARY Number of Participants Experiencing at Least One Grade >=3 Toxicity |
26; 27; 6; 9 | — |
| SECONDARY Rate of Participants Who Were Alive Without Distant Metastases at 1 Year |
79; 70 | — |
| SECONDARY Rate of Participants Who Were Alive Without Distant Metastases at 2 Years |
74; 54 | — |
| SECONDARY Number of Participants Who Achieved at Least Partial Response (Responders) |
26; 25; 6; 11 | — |
| SECONDARY Rate of Participants Who Were Alive Without Loco-regional Failure at 1 Year |
89; 81 | — |
| SECONDARY Rate of Participants Who Were Alive Without Loco-regional Failure at 2 Years |
84; 72 | — |
| SECONDARY Change in Quality of Life Between Baseline and End of Treatment (After 5 to 13 Weeks) |
-9.1; -4.7; -19.2; -13.0; -22.0; -18.1 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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:
- serum creatinine ≤ 1.5 mg/dl
- creatinine clearance ≥ 50 ml/min according to Cockcroft-Gault Formula
- no known allergies against chimeric antibodies
- effective contraception for male and female patients if there is a risk of conception
Exclusion Criteria
- 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)) 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
Data sourced from ClinicalTrials.gov (NCT01787006). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.