p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer: A Multicenter, Randomized Controlled, Predictive Marker Clinical Trial

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: 5-Fluoruracil, Cisplatinum
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br> | Drug: 5-Fluoruracil, Cisplatinum<br>* 5 FU 1000mg/m2; days 1-5; 3 cycles: q21 Cisplatin 80mg/m2; day 1; 3 cycles: q21<br>|
| Experimental: B<br> | Drug: Docetaxel<br>* Docetaxel 75mg/m2, day 1; 3 cycles; q21<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response (clinical and pathological) to neoadjuvant treatment in relation to p53 genotype |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete pathological response and relation to p53 genotype |  | 12 weeks | 
| Complete tumor resection rate |  | 12 weeks | 
| Perioperative morbidity and mortality |  | 16 weeks | 
| Disease free and overall survival and relation to p53 genotype |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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predictive marker, personalized therapy, response assessment, p53 genotype