The primary study objective is to compare the efficacy, as assessed by overall survival, of surgery and neo-adjuvant chemotherapy to surgery alone in patients with resectable liver metastases of colorectal cancer and a high clinical risk score.…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: overall survival (OS), calculated from the date of
randomization to the date of death from any cause of the patient
Secondary outcome
Besides OS, we will evaluate PFS of the patients included in the study. PFS
will be defined counting from the date of randomization to the first event
defined as local recurrence or progression, distant recurrence or death from
any cause. Furthermore:
* To determine quality of life in the two study arms
* To determine treatment response on neoadjuvant chemotherapy
* To compare morbidity of surgery and resection rate between the 2 arms
* To evaluate whether CEA can predict for treatment response, PFS and OS
Background summary
Efforts to improve the outcome of liver surgery by combining the resection with
chemotherapy have failed to demonstrate overall survival (OS) benefit. This
may partly be due to the fact that these studies often involve strict study
protocol inclusion criteria. Consequently, patients with a high Clinical Risk
Score (CRS) - who might benefit the most from chemotherapy - are often
underrepresented in these studies. Since genuine survival benefit has not yet
been demonstrated, could this low impact of chemotherapy on survival then be
explained by the relatively low risk of the patients in these trials? In view
of the retrospective observations that pre-selection of patients by using
prognostic characteristics may define the patient population most likely to
benefit from chemotherapy, it was decided to take CRS stratification as the
base for a randomized controlled trial in resectable patients.
This study will therefore evaluate the impact of neo-adjuvant chemotherapy in
patients with high-risk (CRS 3-5) resectable colorectal liver metastases (CRLM)
without extrahepatic disease. Our hypothesis is that adding neo-adjuvant
chemotherapy to surgery will provide an improvement in OS in this high-risk
patient group.
Study objective
The primary study objective is to compare the efficacy, as assessed by overall
survival, of surgery and neo-adjuvant chemotherapy to surgery alone in patients
with resectable liver metastases of colorectal cancer and a high clinical risk
score. Secondary objectives are to investigate the progression free survival
(PFS) in both arms and Quality of Life (QOL), to investigate morbidity of
resection in both arms and to investigate whether CEA levels can predict for
treatment response PFS
Study design
Randomized, prospective, phase III study
Intervention
Patients will be randomized into one of two groups. One group will be treated
by surgery for the liver metastases only (standard treatment, arm 1). The other
group will be treated by neo-adjuvant oxaliplatin-based chemotherapy, followed
by surgery for the liver metastases (arm 2).
Study burden and risks
Patients who will participate in the study and randomize for arm B
(neo-adjuvant chemotherapy + surgery) are expected to have a better overall
survival compared to the current standard therapy (surgery only). However, the
neo-adjuvant chemotherapy administered in arm B may cause systemic side
effects. The chemotherapy regimen used in arm B is known to be well-tolerated
as the regimen is used as a standard adjuvant treatment in stage 3 colorectal
cancer patients. Unlike non-study patients, all patients participating in the
study will complete Quality of Life questionnaires (QLQ-C30 and MFI) at
baseline and then every 3 months until 1 year after treatment completion.
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
* Age * 18 years.
* ECOG performance status 0 or 1
* Histologically confirmed primary colorectal carcinoma. Primary colorectal carcinomas to be included are:
* Previously resected histologically proven colorectal carcinoma
* Coloncarcinoma still in situ, deemed suitable for resection at the time of liver surgery
* Rectal carcinoma still in situ, requiring no neo-adjuvant radiotherapy, deemed suitable for resection at the time of liver surgery
* Rectal carcinoma still in situ, requiring short-course neo-adjuvant radiotherapy, deemed suitable for resection at the time of liver surgery
* Radiologically confirmed and resectable liver metastasis of colorectal cancer after surgery. Criteria for resectability are outlined in the study protocol.
* Clinical risk score of 3-5
Exclusion criteria
* Prior adjuvant chemotherapy for the primary colorectal carcinoma given <6 months prior to detection of the liver metastases.
* Prior non colorectal malignancies, except for patients with basal or squamous cell carcinoma of the skin, or patients with carcinoma in situ of the cervix.
* Presence of extrahepatic disease
* Locally advanced rectal cancer in situ requiring long-course pre-operative chemoradiotherapy
* Major surgical procedure <4 weeks prior to randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004952-39-NL |
| CCMO | NL47227.078.14 |
| OMON | NL-OMON27498 |