Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04840186 |
| Other study ID # |
167434 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 23, 2021 |
| Est. completion date |
March 2026 |
Study information
| Verified date |
June 2021 |
| Source |
Oslo University Hospital |
| Contact |
John Christian F Glent, MD |
| Phone |
92214992 |
| Email |
uxgloh[@]ous-hf.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Patients with multiple colorectal liver metastases that progress on 1st line chemotherapy
have a very dismal prognosis, and their options are few. Resections are regularly performed
although this is only supported by anecdotal evidence for this patient group. We want to
assess whether resections actually confer benefit as compared to 2nd line chemotherapy alone,
in a randomized controlled trial.
Description:
Colorectal cancer (CRC) is the second most frequent malignant disease in Norway (Cancer in
Norway 2017). About 50% of the patients will have metastatic disease at the time of diagnosis
or develop metastatic disease later on. Liver metastases are the most frequent presentation
of metastatic disease. Liver resection is considered the only curative treatment option in
CRC patients with liver metastases, however only about 20% of the patients are candidates for
liver resection. The treatment option for the majority of the patients is palliative
chemotherapy with a median overall survival from start of chemotherapy of about 2 years, and
only 10-12 months from starting 2nd line chemotherapy.
While high-quality data (randomized trials) is wanting, it is generally accepted that the
only curative treatment for colorectal liver metastases (CRLM) is surgery. Liver resections
are generally well tolerated and safe 1, but some patients recur early and probably have no
benefit from surgery, or even a net loss of quality-of-life (QoL). These are hard to identify
beforehand, but patients with multiple tumours that progress on 1st line chemotherapy are at
high risk of early recurrence following resection2, 3. These patients are in a grey zone:
their metastases may be technically resectable, but the aggressive biology of their disease
makes overall outcome of surgery highly uncertain. The decision to offer resection to some of
these patients primarily results from want of better alternatives and from lack of
sufficiently precise prognostication.
As resections are generally well tolerated and adequate prognostication is wanting, there is
a tendency to offer resections to patients who have borderline resectable CRLM or who exhibit
other non-favourable traits like large or multiple metastases, or progression on 1st line
chemotherapy. Resections followed by early recurrence represent a net loss of quality-of-life
and an unwanted expenditure for society. Exploring the optimal treatment modality for
patients in this grey zone, i.e. with uncertain benefit from surgery, is important to provide
optimal treatment for patients in a critical situation.
Palliative chemotherapy is in general the only treatment option for the vast majority of
non-resectable patients. The expected median overall survival (OS) from start of first line
chemotherapy is about 2 years and the 5 years OS is about 10%, although longer median OS has
been obtained in selected patients with good performance status (ECOG 0-1), no (K)RAS or BRAF
mutations and left-sided tumours 4-8. The OS from start of second line chemotherapy however
is only 10-12 months 9. This places the prognosis for this group of cancer patients on par
with those having pancreatic cancer.
This trial targets a group of patients that are not eligible for the Excalibur 1 and 2 trials
but still have as dismal or even worse prognosis. They will - according to the inclusion
criteria - have a large tumour burden and have shown progression on 1st line systemic
chemotherapy treatment. Based on previous trials, only 30 % of this patient group are
estimated to be alive after two years. These patients have today only one treatment modality
available: 2nd line systemic chemotherapy. Response can, however, only be expected in a small
minority.
With such a dismal outcome for these patients, almost any attempt to improve survival would
be warranted and anecdotal evidence shows that some appear to benefit substantially. This
may, however, be a result of biased selection and the benefit of surgery in this grey zone is
unproven.
