p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer

Phase 3

Completed

Brief Summary: Study Hypothesis:

PANCHO is a prospective randomized, predictive marker study, evaluating the interaction between the potential predictive marker 'p53 genotype' and response to induction chemotherapy in patients with esophageal cancer considered resectable.

170 patients with measurable disease will be enrolled in this study. After testing the marker genotype (two genotypes: p53 normal or p53 mutant) patients will be stratified according to histological subtype only (adeno- or squamous cell carcinoma) and will be randomly assigned to receive 3 cycles of either 5-fluorouracil (5FU)/cisplatin or docetaxel monotherapy as neoadjuvant therapy. All patients will be rendered to subsequent surgery in order to assess both clinical and pathohistological response.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
A	5-Fluoruracil, Cisplatinum	-
B	Docetaxel	-

Primary Outcome Measures

Name	Time	Method
Tumor response (clinical and pathological) to neoadjuvant treatment in relation to p53 genotype	12 weeks

Secondary Outcome Measures

Name	Time	Method
Disease free and overall survival and relation to p53 genotype	2 years
Complete pathological response and relation to p53 genotype	12 weeks
Complete tumor resection rate	12 weeks
Perioperative morbidity and mortality	16 weeks

Locations (13): SMZ OST
🇦🇹
Vienna, Austria
Landesklinikum Wiener Neustadt
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Wiener Neustadt, Lower Austria, Austria
Landesklinikum St. Pölten
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St. Polten, Lower Austria, Austria
Wilhelminenspital
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Vienna, Austria
Landesklinikum Feldkirch
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Feldkirch, Vorarlberg, Austria
Krankenhaus der Elisabethinen
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Linz, Austria
Krankenhaus der Barmherzigen Brüder
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Stankt Veit, Austria
Hanusch Krankenhaus
🇦🇹
Vienna, Austria
Medical University Innsbruck
🇦🇹
Innsbruck, Tirol, Austria
Rudolfstiftung
🇦🇹
Vienna, Austria
Landeskrankenhaus Leoben
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Leoben, Austria
Medical University of Vienna
🇦🇹
Vienna, Austria
Kaiser Franz Josef Spital
🇦🇹
Vienna, Austria