The metastatic lesions may be very different from the primary tumor because of intrinsic tumor heterogenity, clonal selection through metastatic process and following previous cytotoxic treatments. Metastatic tumor harboring actionable targets or signaling pathways may respond to inhibitory agents directed against specific aberrations irrespective of tumor origin. In the MetAction study, patients will receive therapy based on molecular aberrations in the metastatic lesions, actionable target identification (ATI), rather than on histological tumor type.

The ATI rate in an unselected metastatic patient population is uncertain, and response rates associated with ATI based targeted therapy have hardly been reported. In this perspective, The MetAction study is essentially a feasibility study aiming to tailor metastatic cancer therapy based on genomic profiles.

Recognizing the rapidly increasing number of drugs targeting specific molecular aberrations in cancer, it is necessary to define rational strategies to make such treatment available to Norwegian cancer patients.These targeted drugs are extremely costly and have significant side effects, although presumably to a lesser extent than many of the classic cytotoxic drugs available. Thus, in the interest of the patient in question and the society in general, it is important to give the right drug to the right patient and to the presumably right time in the disease course.

Hitherto, most of the drugs in question are given in the palliative setting, i.e. to patients with disseminated metastatic disease. The metastatic lesion may be very different from the primary tumor, and hence, it is rational to analyze the tumor to be treated, the metastatic lesion(s), for the presence of molecular aberrations, rather than basing treatment decisions on molecular features known to be present in a particular tumor type or in the primary tumor.

Inclusion Criteria:

• Metastatic cancer and progression by RECIST 1.0 evaluated by internal review on at least one prior regimen of established palliative systemic therapies for advanced disease and eligibility for repeat biopsy sampling. The patient must have received ≥6 weeks of the previous treatment. Only patients who have no other standard treatment option or were the treatment option is considered to offer the patients only minor benefit may be included in the study.
• Radiological evaluation intervals on last prior therapy (period A) must have been 6 to 12 weeks.
• At least one measurable lesions (>10mm on CT-scan) according to RECIST 1.0.
• Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 1 or lower.
• Life expectancy of more than 3 months.
• Adequate bone marrow function without current use of colony-stimulating factors: Neutrophils ≥1.5 x109/l; Platelets ≥100 x109/l; Hb >10 g/dl, INR within normal level.
• Adequate liver function: AST/ALT ≤5x ULN; Bilirubin ≤2x ULN, albumin >30 g/l.
• Adequate renal function: Creatinine ≤1.5x ULN.
• Be able to use recommended dose of the selected targeted therapy as described in the drug specific SPC.
• Be able to comply with the protocol.
• Fertile men and women must be willing to use effective contraceptives.
• Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures.

Exclusion Criteria:

• Metastatic disease from more than one malignancy.
• Untreated or symptomatic brain metastasis (patients must be symptom-free without the use of corticosteroids).
• Any reason why, in the opinion of the investigator, the patient should not participate.
• Pregnancy.
• Breastfeeding
• Anticoagulation with coumarin derivatives.
• Radiation therapy within 4 weeks of start of treatment.
• Need to use medications contraindicated according to SPC of the different drugs.