p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer

PANCHO will test the hypothesis that p53 genotype is predictive for response to chemotherapy. The study uses the marker by treatment interaction design. In this design, we assume that the status of the marker splits the whole population into two distinct groups (p53 normal versus p53 mutant).

Patients in each marker group are randomly assigned to two different treatments, and planned statistical analysis is to test whether one treatment is superior to the other within each marker group separately.

The marker information but not the treatment is blinded to the patient and the investigators.

Inclusion criteria

• Histological verification of esophageal cancer
• Presence of T2,T3,T4 or any N1 (except M1)
• Clinically measurable lesions according to RECIST criteria
• Males and females, age >18 to 75 or older with WHO performance status 1
• No prior tumor therapy for esophageal cancer
• No other malignancy in history within 5 years before evaluation
• Performance status of 0-2 on ECOG scale
• Medical fitness (adequate for possible esophageal resection, adequate organ function: see protocol)
• Signed informed consent
• Males and females with reproductive potential must use an approved contraceptive method. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

Exclusion criteria

• Inoperability (technical or functional)
• Clinical stage cT1N0, any M1
• Treatment with any of the investigational drugs within the last 6 months
• Concurrent administration of any other tumor therapy
• Pregnancy, breast feeding
• Serious concomitant disorders that would compromise the safety of the patient or ability to complete the study
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment