To determine the median progression-free survival (PFS) and R0/1 secondary resection rate upon induction systemic treatment in colorectal cancer patients with initially unresectable liver-only metastases, stratified by RAS and BRAF tumor mutation…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression free survival (PFS).
Secondary outcome
- R0/1 resection rate
- Median overall survival
- 3- and 5-year overall survival rates
- Tumor response rate
- Toxicity
- Pathological complete response rate (pCR) of resected lesions
- Postoperative morbidity.
Background summary
Colorectal cancer patients with initially unresectable liver-only metastases
may be cured after downsizing of metastases by induction systemic therapy.
However, the optimal induction regimen has not been defined, and no consensus
exist on criteria for resectability.
Study objective
To determine the median progression-free survival (PFS) and R0/1 secondary
resection rate upon induction systemic treatment in colorectal cancer patients
with initially unresectable liver-only metastases, stratified by RAS and BRAF
tumor mutation status and location.
Study design
Colorectal cancer patients with initially unresectable liver-only metastases,
as prospectively confirmed by an expert panel according to predefined criteria,
will be tested for RAS and BRAF tumor mutation status. Patients with RAS or
BRAF mutant tumors and right-sided localised tumors will be randomised between
doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab (schedule 1), and
triple chemotherapy (FOLFOXIRI) plus bevacizumab (schedule 2). Patients with
RAS and BRAF wildtype and left-sided localised tumors will be randomized
between doublet chemotherapy (FOLFOX or FOLFIRI) plus either bevacizumab
(schedule 1) or panitumumab (schedule 3).
Patient imaging will be reviewed for resectability by a central panel,
consisting of at least one radiologist and three surgeons every assessment.
Central panel review will be performed prior to randomization as well as during
treatment, as described in the protocol.
Intervention
*Schedule 1: 5-fluorouracil, oxaliplatin (FOLFOX) or 5-fluorouracil, irinotecan
(FOLFIRI), both combined with bevacizumab
*Schedule 2: 5-fluorouracil, oxaliplatin, irinotecan (FOLFOXIRI) and bevacizumab
*Schedule 3: FOLFOX or FOLFIRI, both combined with panitumumab
Study burden and risks
- Chemotherapy cycles of 2 weeks
- Every 8 weeks CT scan
- All studies will be perfomed on tissue that has already been obtained from
patients for diagnostic purposes. No tissue will be collected with the sole
purpose of research.
Schenkkade 50 suite 17
Den Haag 2595 AR
NL
Schenkkade 50 suite 17
Den Haag 2595 AR
NL
Listed location countries
Age
Inclusion criteria
- Histologically proven colorectal cancer , - unresectable metastases confined
to the liver according to CT scan, obtained <= 2 weeks prior to registration.
Unresectability will be confirmed by the panel. Patients with small (<= 1 cm)
extrahepatic lesions that are not clearly suspicious of metastases are
eligible., - RAS/BRAF mutation status known, - WHO performance status 0-1
(Karnofsky performance status >= 70), - Age >= 18 years, - No contraindications
for liver surgery, - In case of primary tumor in situ: tumor should be
resectable
- In case of resected primary tumor: adequate recovery from surgery, - Adequate
organ functions, as determined by normal bone marrow function (Hb ³ 6.0 mmol/L,
absolute neutrophil count ³ 1.5 x 109/L, platelets ³ 100 x 109/L), renal
function (serum creatinine <= 1.5x ULN and creatinine clearance, Cockroft
formula, ³ 30 ml/min), liver function (serum bilirubin <= 2 x ULN, serum
transaminases <= 5x ULN), - Life expectancy 12 weeks or more, - Expected
adequacy of follow-up, - Written informed consent
Exclusion criteria
- Extrahepatic metastases, with the exception of small (<= 1 cm) extrahepatic
lesions that are not clearly suspicious for metastases , - Unresectable primary
tumor, or resectable tumor requiring immediate surgery, - Serious comorbidity
or any other condition preventing the safe administration of study treatment
(including both systemic treatment and surgery), - Major cardiovascular events
(myocardial infarction, severe/unstable angina, congestive heart failure, CVA)
within 12 months before registration, - Uncontrolled hypertension, or
unsatisfactory blood pressure control with >=3 antihypertensive drugs, -
Previous systemic treatment for metastatic disease; previous adjuvant treatment
is allowed if completed >= 6 months prior to registration, - Previous surgery
for metastatic disease, - Previous intolerance of study drugs in the adjuvant
setting, - Pregnant or lactating women, - Second primary malignancy within the
past 5 years with the exception of adequately treated in situ carcinoma of any
organ or basal cell carcinoma of the skin
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-005435-24-NL |
| ClinicalTrials.gov | NCT02162563 |
| CCMO | NL47650.018.14 |