Total Neoadjuvant Treatment Without Surgery For Locally Advanced Rectal Cancer (NO-CUT)
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|ClinicalTrials.gov Identifier: NCT03565029|
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : September 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Colo-rectal Cancer||Drug: XELOX Radiation: Radiotherapy||Phase 2|
Colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer death in Europe. Rectal cancer accounts for about 25-30% of all colorectal cancer diagnoses. Five-year survival rates depend on stage at diagnosis, about 92% for stage I, 87% for stage II A, 63% for stage II B, 89% for stage III A, 69% for stage III B, and for stage III C cancers the survival rate is about 53%; stage IV rectal cancers have a 5-year relative survival rate of about 11%. With the chemoradiation therapy (CRT), the resulting pathologic complete response (pCR) across all stages has been documented in up to 30% of patients. Most importantly, patients achieving pCR have lower rates of tumor recurrence, and improved survival, compared to those who do not achieve pCR. Moreover, data from the National Surgical Quality Improvement Project document a 35% risk of morbidity associated with both low anterior and abdominoperineal resection. Long-term morbidity includes bowel and bladder incontinence, sexual dysfunction, and complications associated with temporary and permanent stomas.
Due to the observation of the absence of residual tumor in the pathological specimens of a significant proportion of patients treated with CRT for local or locally advanced rectal cancer, in the early-2000s, two clinical issues arose: firstly, if pCR could be predicted after CRT with clinical, radiological, or endoscopic restaging assessment thus defining clinical complete response (cCR); and secondly if patients with cCR should necessarily undergo radical surgery to achieve cure at the cost of morbidity, mortality, and functional consequences associated with radical rectal surgery. Consequently, an increasing number of reports suggested that non-operative management (NOM), consisting of close surveillance of patients with cCR, could be an acceptable alternative to rectal surgery (proctectomy). Led by small prospective series published since the late 90's by Habr-Gama and colleagues, several small international series have reported similar oncologic outcomes in cCR patients followed by close active surveillance (the so-called watch-and-wait (W&W) or NOM approach) compared to those treated with radical surgery.
Between 2011 and 2013 a NOM approach was carried out in 31 patients achieving cCR out of 259 (12%). In their analysis, a further 98 patients, selected from a United Kingdom regional registry, similarly managed from 2005 to 2015, were added to the NOM group (129 patients). Overall Survival and Disease Free Survival rates resulted at least comparable to that of patients treated with standard surgery following neo-adjuvant CRT.
On the other hand, these small single institution pilot studies have been conducted enrolling small cohorts of patients with less than 500 patients having been evaluated worldwide. A high variability in stage at diagnoses, local recurrence rate, distant recurrence rate (0-60% and 0-17%, respectively) and type and outcome of salvage therapy (0 to 100%) have been reported and no reliable data on long term outcomes are available. Based on these limitations, the NOM of rectal cancer deserves consideration within purposely designed clinical trials.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||one-stage phase II trial seeking to establish whether an oxaliplatin-based chemotherapy preceding standard neo-adjuvant fluoropyrimidines-based chemo radiotherapy, can safely spare demolitive surgical intervention in patients with operable rectal cancer, without increasing the risk of distant relapse. The trial also has a translational component aimed at establishing whether selected genomic, epigenetic, and transcriptomic markers are predictive of tumor and patient outcome.|
|Masking:||None (Open Label)|
|Official Title:||Total Neoadjuvant Treatment Without Surgery For Locally Advanced Rectal Cancer: Prospective Clinical Trial To Assess Tumor Complete Response, Circulating Tumor Genetic And Epigenetic Biomarkers, And Stromal Transcriptome To Interpret Clinical Outcome|
|Actual Study Start Date :||June 1, 2018|
|Estimated Primary Completion Date :||October 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Medium/low locally advanced rectal cancer
Patients with Stage II (cT3-4 N0) or Stage III (cT1-4, N1-3) locally advanced rectal cancer amenable to Total Mesorectal Excision (TME)/Abdominal-Perineal Amputation
Capecitabine and Oxaliplatin (4x cycles)
- Distant Relapse-Free Survival (DRFS) [ Time Frame: 2.5 years ]Disease free survival rate
- Clinical complete response rate [ Time Frame: 2 months ]Clinical complete response rate
- Local recurrence and organ preservation rate [ Time Frame: 6 months ]Local recurrence and organ preservation rate
- Colostomy-free survival [ Time Frame: 6 months ]Colostomy-free survival
- Overall survival [ Time Frame: 2.5 years ]Overall survival
- Patient reported outcomes [ Time Frame: 2.5 years ]European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-C30 and its colorectal cancer specific module Quality of Life Questionnaire-38)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565029
|Contact: Salvatore Siena, MD||+396444 ext firstname.lastname@example.org|
|Contact: Andrea Sartore Bianchi, MD||+396444 ext email@example.com|