p53 and Response to Preoperative Radiotherapy for T2 and T3

NCT ID: NCT02140723

Last Updated: 2022-04-07

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2023-12-31

Brief Summary

Background:

Meta-analyses of large randomized trials proved the superiority of preoperative short course radiation and surgery, as compared with surgery alone. Short course radiation results in a 50% reduction in terms of local relapse in stage II and III rectal cancer patients. Patients with complete pathological remission additionally show a significant survival benefit. Complete pathological remission (pCR) occurs in 8% after preoperative radiation and in >16% if the interval between radiation and surgery is at least 8 weeks.

It is generally accepted that mutations in the TP53 gene represent a crucial defect in the apoptosis pathway. Radiation therapy is suggested to act via induction of apoptosis in irradiated cells. Therefore, it is expected that a defect in the TP53 gene has an effect on the success of radiation therapy.

Currently available imaging tools are hardly able to diagnose response to radiation therapy correctly, as this does not essentially correlate with tumor size.

Method:

Aim of this prospective observation study is to strengthen the hypothesis that the TP53 genotype is a promising marker to predict response to radiation therapy in rectal cancer patients. Consequently, the expected results will justify prospective, randomized intervention trials to obtain level of evidence I for the p53 marker hypothesis. Trial endpoint is downstaging and pCR rate. Tumor stage and pathological remission will be evaluated by MRT and pathohistology and correlated to the TP53 genotype of the diagnostic biopsy. Additionally, we will investigate the applicability of novel imaging modalities in magnet resonance tomography to monitor response to radiotherapy.

The objective of this study is

• to evaluate the effect of a genetic tumor marker (TP53 genotype) on the response to preoperative short course radiation (in terms of downstaging and pCR rate)
• to evaluate the applicability of novel magnet resonance tomography imaging modalities to monitor response to preoperative short time radiation.

Conclusion:

The prospective evaluation of the potential predictive marker TP53 may bring us one-step closer to an individualized therapy regimen, which allows the restriction of preoperative radiation in rectal cancer to those patients who will benefit.

Conditions

Rectal Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

preoperative short course radiation

preoperative short course radiation with 8 weeks delay of surgery

preoperative short course radiation

Intervention Type: RADIATION

Interventions

preoperative short course radiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

Patients who are eligible for this observational study will be treated according to current standards with preoperative short course radiation (5x5 Gy) and a subsequent interval to surgery of at least 8 to maximum 16 weeks.

According to standards of rectal cancer therapy, eligible patients will meet the following criteria:

• Histologically confirmed adenocarcinoma of the rectum
• Tumor staging with MRI
• Inferior margin of the tumor located not farther than 15 cm from anal verge and below the level of S1-2
• Tumor stage T2 and T3
• No evidence of metastatic disease
• No prior tumor therapy for rectal or pelvic cancers (surgery, radio-, chemo-, immunotherapy, molecular target therapy, or any other type of tumor therapy)
• Medical fitness of the patient for treatment (decided by the involved physician)
• Patient compliance
• Signed informed consent from the patient or a legal representative, for the analysis of the tumor including genetic analyses of the tumor DNA.

Exclusion Criteria

Patients will be excluded from the study for any of the following reasons

• Clinical stage T1 (appropriate for local excision),
• Clinical stage T4 (Radio/Chemotherapy)
• Clinical stage M+ (distant metastases)
• No tumor staging with MRI
• Inoperability (technical or functional)
• Prior tumor therapy of the pelvis
• Concurrent administration of any other tumor therapy
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
• Serious concomitant disorders or attitudes of the patient that would compromise the safety of the patient or his/her ability to complete the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Daniela Kandioler

Unif. Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniela Kandioler, MD

Role: STUDY_CHAIR

MUW

Locations

Medical University of Vienna, Department of Surgery

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Daniela Kandioler, MD

Role: CONTACT

daniela.kandioler@meduniwien.ac.at

+43 1 40400 56210

References

Kandioler D, Zwrtek R, Ludwig C, Janschek E, Ploner M, Hofbauer F, Kuhrer I, Kappel S, Wrba F, Horvath M, Karner J, Renner K, Bergmann M, Karner-Hanusch J, Potter R, Jakesz R, Teleky B, Herbst F. TP53 genotype but not p53 immunohistochemical result predicts response to preoperative short-term radiotherapy in rectal cancer. Ann Surg. 2002 Apr;235(4):493-8. doi: 10.1097/00000658-200204000-00006.

Reference Type: BACKGROUND

PMID: 11923604 (View on PubMed)

Related Links

http://www.p53.at

Homepage of the p53-research group

Other Identifiers

PART1

Identifier Type: -

Identifier Source: org_study_id