Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

Inclusion Criteria: (screening step - non-drug specific)

• Adult (≥ 18 yrs) patient with a histologically-proven incurable metastatic solidtumour (excluding primary brain tumours), multiple myeloma or B cell non-Hodgkinlymphoma (excluding CLL, SLL and HCL), for whom there is no standard treatment knownto prolong life, or who has refused such treatment.

• ECOG performance status 0-2.

• Patients must have normal organ function as follows:

• Absolute neutrophil count: ≥ 1.5 x 10^9/L for solid tumours; ≥ 1.0 x 10^9/L forneurologic malignancies

• Platelets ≥ 75 x 10^9/L (or ≥ 50 x 10^9/L if bone marrow involvement by myelomaor lymphoma).

• Total bilirubin ≤ 1.5 x UNL.

• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal value unlessliver metastases are present in which case they must be < 5 x ULN;

• Serum creatinine ≤ 1.5 x UNL or calculated or measured creatinine clearance ≥ 50mg/min/1.73µ^2

• Patients must have measurable disease

• Results must be available from tumour genomic or protein expression testing (if usedto identify genetic variants), from one of the initiatives / groups listed inprotocol Appendix VII. The test may have been performed on the primary tumour or ametastatic deposit (including bone marrow), or blood, in a diagnostic or researchlaboratory and must reveal a potentially actionable variant.

• Patient consent (Main Study Consent for the screening step) must be appropriatelyobtained in accordance with applicable local and regulatory requirements. Eachpatient must sign a consent form prior to the screening step to document theirwillingness to participate

• Patients must be accessible for treatment and follow-up. Patients registered on thistrial must be treated and followed at the participating centre or a CCTG IND site.This implies there must be reasonable geographical limits (for example: 1 ½ hour'sdriving distance) placed on patients being considered for this trial.

• Women/men of childbearing potential must have agreed to use a highly effectivecontraceptive method.

Exclusion Criteria: (screening step - non-drug specific)

• Patients with prior or concurrent malignancy whose natural history or treatment hasthe potential to interfere with the safety or efficacy assessment of theinvestigational regimen.

• Patients with ongoing toxicity ≥ CTCAE grade 2, other than peripheral neuropathy orasymptomatic, corrected biochemical toxicities (e.g. hypothyroidism corrected bythyroid replacement), related to prior anti-tumour treatment. Patients with ongoingperipheral neuropathy of ≥ CTCAE grade 3 will be excluded.

• Patients concurrently receiving any other anti-cancer therapy (cytotoxic, biologic,radiation, or hormonal other than for replacement) except for medications that areprescribed for supportive care but may potentially have an anti-cancer effect (e.g.megestrol acetate, bisphosphonates) or ongoing castration-intent therapy forprostate cancer. These medications must have been started ≥ one month prior toenrollment on this study. Patients may be on warfarin, low molecular weight heparinor direct factor Xa inhibitors, unless such therapies are prohibited bydrug-specific ineligibility criteria.

• Patients with known active progressive brain metastases. Patients with previouslytreated brain metastases are eligible, provided that the patient has not experienceda seizure or had a clinically significant change in neurological status within onemonth prior to screening. All patients with previously treated brain metastases mustbe stable (clinically and radiologically) for at least one month after completion oftreatment and either off steroid treatment or only taking physiological doses ofsteroids prior to the screening step.

• Patients with clinically significant pre-existing cardiac conditions, includinguncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias,or symptomatic congestive heart failure.

• Patients with known left ventricular ejection fraction (LVEF) < 40%.

• Patients with stroke (including TIA) or acute myocardial infarction within threemonths prior to the screening step.

• Patients with acute gastrointestinal bleeding within one month prior to thescreening step.

• Patients with any other clinically significant medical condition which, in theopinion of the treating physician, makes it undesirable for the patient toparticipate in the study or which could jeopardize compliance with studyrequirements including, but not limited to: ongoing or active infection, significantuncontrolled hypertension, or severe psychiatric illness/social situations.

• Lactating and nursing women

• Patients who do not meet drug-specific eligibility requirements for the drugselected by the treating physician.