Rectal CancerPART1NCT02140723
p53 and Response to Preoperative Radiotherapy for T2 and T3
An observational study of Rectal Cancer, run by Medical University of Vienna at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- preoperative short course radiation
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteAustria
- Study dates
- Aug 2011to Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Rectal cancer patients with clinical staging T2/T3 Nx M0
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna, Department of Surgery
Vienna, 1090
About this study
Official title: PART1 - a Prospective Phase II Study to Evaluate the Impact of TP53 Gene Mutations in Patients With Preoperative Radiotherapy for T2 and T3 Rectal Cancer
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.
Read more
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
- Being tested
- preoperative short course radiation
- Keywords
- preoperative short course radiotherapy, delay of surgery, rectal cancer, TP53, predictive marker, MRT imaging
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
preoperative short course radiationRadiation
| Study group | Role | What they receive |
|---|---|---|
| preoperative short course radiation | preoperative short course radiation with 8 weeks delay of surgery Receives: Radiation: preoperative short course radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interaction between the status of the biomarker TP53 and response to treatment
Primary outcome measure is the interaction between the status of the biomarker TP53 and response to radiation.
The TP53 maker status is determined by standardized gene specific sequencing of the TP53 using DNA from formalin fixed paraffin embedded material from diagnostic biopsies.
Response to treatment is determined by "down sizing" - down sizing will be measured by comparison of pretreatment T stage with pathohistological post treatment T stage . Pretreatement T stage is assessed with MRI, and supported by endosonography. Posttreatment T stage will be assessed prior to operation with MRI and after resection in the pathohistological specimen. The postreatment MRI results will be compared pathohistology.
Measured: weeks 12-16 after treatment
Secondary outcomes (4)
pCR rate
pCR - pathohistological complete resmission as assessed in surgical specimen
Measured: 12-16 weeks after treatment
complete resection rate
Patholohistological assessment
Measured: 12-16 weeks after treatment
relapse
local and distant relapse
Measured: 3 years
overall survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2014 (estimated)
- Study startAug 2011
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniela Kandioler, Medical University of Vienna
- Investigators
- Daniela Kandioler, MD, Study chair, MUW
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02140723
- Sponsor's protocol ID
- PART1
- Acronym
- PART1
- Status last verified
- Apr 2022
- First submitted
- 30 Apr 2014
- Last updated
- 7 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11923604
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PART1 - a Prospective Phase II Study to Evaluate the Impact of TP53 Gene Mutations in Patients With Preoperative Radiotherapy for T2 and T3 Rectal Cancer
- ClinicalTrials.gov ID
- NCT02140723
- Acronym / sponsor ID
- PART1 / PART1
- Conditions
- Rectal Cancer
- Keywords
- preoperative short course radiotherapy, delay of surgery, rectal cancer, TP53, predictive marker, MRT imaging
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 16 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| preoperative short course radiation | – | Radiation: preoperative short course radiationpreoperative short course radiation with 8 weeks delay of surgery |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Rectal cancer patients with clinical staging T2/T3 Nx M0
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| preoperative short course radiation | Radiation | preoperative short course radiation |
Primary outcome
Interaction between the status of the biomarker TP53 and response to treatment
Time frame: weeks 12-16 after treatment
Primary outcome measure is the interaction between the status of the biomarker TP53 and response to radiation. The TP53 maker status is determined by standardized gene specific sequencing of the TP53 using DNA from formalin fixed paraffin embedded material from diagnostic biopsies. Response to treatment is determined by "down sizing" - down sizing will be measured by comparison of pretreatment T stage with pathohistological post treatment T stage . Pretreatement T stage is assessed with MRI, and supported by endosonography. Posttreatment T stage will be assessed prior to operation with MRI and after resection in the pathohistological specimen. The postreatment MRI results will be compared pathohistology.
4 secondary outcomes
pCR rate
Time frame: 12-16 weeks after treatment
complete resection rate
Time frame: 12-16 weeks after treatment
relapse
Time frame: 3 years
overall survival
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
- Background: PubMed 11923604Kandioler 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.
- Homepage of the p53-research groupLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniela Kandioler, MD study chair
MUW
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectal Cancer, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Daniela Kandioler, MD (+43 1 40400 56210, daniela.kandioler@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interaction between the status of the biomarker TP53 and response to treatment (time frame: weeks 12-16 after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02140723, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2022.