Clinical trial NCT00525200: p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer
Official title: p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer: A Multicenter, Randomized Controlled, Predictive Marker Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Esophageal Cancer
Keywords: predictive marker
personalized therapy
response assessment
p53 genotype
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
name: Austrian Society Of Surgical Oncology
First posted: 2007-09-05
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor response (clinical and pathological) to neoadjuvant treatment in relation to p53 genotype
timeFrame: 12 weeks
Secondary outcomes:
measure: Complete pathological response and relation to p53 genotype
timeFrame: 12 weeks
measure: Complete tumor resection rate
timeFrame: 12 weeks
measure: Perioperative morbidity and mortality
timeFrame: 16 weeks
measure: Disease free and overall survival and relation to p53 genotype
timeFrame: 2 years
Other outcomes:
Locations:
city: St. Polten
country: Austria
facility: Landesklinikum St. Pölten
state: Lower Austria
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
state: Lower Austria
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
state: Tirol
city: Feldkirch
country: Austria
facility: Landesklinikum Feldkirch
state: Vorarlberg
city: Leoben
country: Austria
facility: Landeskrankenhaus Leoben
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen
city: Stankt Veit
country: Austria
facility: Krankenhaus der Barmherzigen Brüder
city: Vienna
country: Austria
facility: Rudolfstiftung
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Kaiser Franz Josef Spital
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Vienna
country: Austria
facility: SMZ OST
city: Vienna
country: Austria
facility: Wilhelminenspital
Study officials:
affiliation: ASSO Representative, MUW, p53research Head
name: Daniela Kandioler, Prof., MBA
role: STUDY_CHAIR
affiliation: Medical University of Vienna, MUV
name: Johannes Zacherl, Prof.
role: STUDY_DIRECTOR
affiliation: MUW
name: Michael Hejna, Prof.
role: STUDY_DIRECTOR
References:
citation: Kandioler D et al. p53 adapted neoadjuvant therapy for esophageal cancer: pilot study. JCO, vol 25, 18S: 206s