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Treatment Strategies in Colorectal Cancer Patients With Initially Unresectable Liver-only Metastases

Sponsored by Dutch Colorectal Cancer Group

About this trial

Last updated 3 years ago

Study ID

CAIRO5

Status

Recruiting

Type

Interventional

Phase

Phase 3

Placebo

No

Accepting

18-75 Years
18+ Years
All
All

Not accepting

Not accepting
Healthy Volunteers

Trial Timing

Started 11 years ago

What is this trial about?

Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and no consensus exist on criteria for resectability. In this study 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 and selected by location of primary tumor. Patients with RAS or BRAF mutant and/or right sided 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 primary 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.

What are the participation requirements?

Yes

Inclusion Criteria

- Histological proof of colorectal cancer

- Initially unresectable metastases confined to the liver according to CT scan, obtained ≤3 weeks prior to registration. Unresectability should be confirmed by the liver expertpanel. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible

- Known mutation status of RAS and BRAF

- 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 ≥ 6.0 mmol/L, absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, ≥ 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 5x ULN)

- Life expectancy > 12 weeks

- Expected adequacy of follow-up

- Written informed consent

No

Exclusion Criteria

- Extrahepatic metastases, with the exception of small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases

- Unresectable primary tumor

- 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 randomisation

- 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 randomisation

- 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, or second primary colorectal cancer.

- Any concomitant experimental treatment.

Locations

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Status

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