Improving Public Cancer Care by Implementing Precision Medicine in Norway

Inclusion Criteria20

• Type of Participant and Health status
• Patient with a pathology-proven locally advanced or metastatic malignant disease who is no longer benefitting from standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated.
• ECOG performance status 0-2.
• For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
• Absolute neutrophil count ≥ 1.5 x109 / L
• Hemoglobin > 9 g/dl
• Platelets > 75,000/µl
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT) and ALT(SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases)
• Calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2.
• Patients must have measurable or evaluable disease. RECIST v1.1 (10, 18) will be used for patients with solid tumours. For patients with multiple myeloma or non-Hodgkin lymphoma, IMWG response criteria (19) and CHESON/Lugano guidelines (20) will be used, resp. For glioblastoma patients, RANO criteria will be used (21). iRECIST will be used for immunotherapy-cohorts. IWG response criteria will be used for haematological cancers.
• Patients whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumour marker only) are NOT eligible, with the exception of CA-125 for ovarian cancer and PSA for prostate cancer (22).
• Results must be available from a genomic / molecular test performed in a preapproved laboratory (Section 10.15). The test used to qualify a patient for participation in IMPRESS-Norway may have been performed on any specimen of the patient's tumour obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed as defined in Section 10.5. NGS analyses will be performed on a newly sampled biopsy if possible. Information from these analyses might be used upon progression, for evaluation of possible new cohort-inclusion.
• Have a genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit see Section 4.3.5
• Note: Eligible genomic tests may include any of the following technologies and equivalent techniques: Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) (incl nanostring), array-based copy number analysis (CNV), sanger sequencing (SS), RNA sequencing, gene panels or whole exome sequencing (WES) by next generation sequencing (NGS). The test may have been performed on a fresh (frozen or in RNA-later) or paraffin-embedded specimen of the primary tumour or a metastatic deposit or on cell-free DNA derived from liquid biopsies (like for instance peripheral blood plasma), as determined by the treating physician, and must reveal a potentially actionable genomic variant or protein overexpression as defined in Section 4.3.
• Patients must meet drug-specific eligibility requirements for the drug selected by the investigator.
• Sex and Contraceptive/Barrier Requirements 9.8. Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate highly effective methods of contraception for the duration of study participation, and for 4 to 24 months following completion of study therapy as defined in Section 11.4.
• 9. Female participants must have a negative highly sensitive pregnancy test <1 month prior to inclusion.
• 10. Male patients should avoid impregnating a female partner. Male study patients must agree to one of the following: practice effective barrier contraception as described under sec. 11.4 during the entire study treatment period and through a certain time after the last dose of study drug. Details are given in the "Drug specific amendment".
• Informed Consent 12.11. Ability to understand and the willingness to sign a written informed consent/assent document as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Guardians / parents can act on behalf of children.