Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03565029 |
| Other study ID # |
2017-003671-60 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2018 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
September 2020 |
| Source |
Niguarda Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
NO-CUT is a 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.
Description:
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.
