Recent advances in laboratory technology have enabled the identification of changes in the
genetic makeup of tumors that might be responsible for their malignant behavior such as
uncontrolled growth and spread. Some of these changes can be 'druggable', i.e. there may be
cancer medicines that can specifically act on the tumour's genetic abnormality. Several
cancer centers and programs have initiated this type of molecular profiling across Canada,
with the goal to identify 'druggable' changes in tumors to find matching therapy for
patients. These include initiatives in British Columbia, Ontario and Quebec. The CAnadian
Profiling and Targeted agent Utilization tRial (CAPTUR) will test the activity of a list of
commercially available targeted agents in patients who have undergone tumor profiling and
have 'druggable' changes identified in their cancers.
Inclusion Criteria: (screening step - non-drug specific)
- Adult (≥ 18 yrs) patient with a histologically-proven incurable metastatic solid
tumour (excluding primary brain tumours), multiple myeloma or B cell non-Hodgkin
lymphoma (excluding CLL, SLL and HCL), for whom there is no standard treatment known
to 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 for
neurologic malignancies
- Platelets ≥ 75 x 10^9/L (or ≥ 50 x 10^9/L if bone marrow involvement by myeloma
or lymphoma).
- Total bilirubin ≤ 1.5 x UNL.
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal value unless
liver 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 used
to identify genetic variants), from one of the initiatives / groups listed in protocol
Appendix VII. The test may have been performed on the primary tumour or a metastatic
deposit (including bone marrow), or blood, in a diagnostic or research laboratory and
must reveal a potentially actionable variant.
- Patient consent (Main Study Consent for the screening step) must be appropriately
obtained in accordance with applicable local and regulatory requirements. Each patient
must sign a consent form prior to the screening step to document their willingness to
participate
- Patients must be accessible for treatment and follow-up. Patients registered on this
trial 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's
driving distance) placed on patients being considered for this trial.
- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method.
Exclusion Criteria: (screening step - non-drug specific)
- Patients with prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen.
- Patients with ongoing toxicity ≥ CTCAE grade 2, other than peripheral neuropathy or
asymptomatic, corrected biochemical toxicities (e.g. hypothyroidism corrected by
thyroid replacement), related to prior anti-tumour treatment. Patients with ongoing
peripheral 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 are
prescribed for supportive care but may potentially have an anti-cancer effect (e.g.
megestrol acetate, bisphosphonates) or ongoing castration-intent therapy for prostate
cancer. These medications must have been started ≥ one month prior to enrollment on
this study. Patients may be on warfarin, low molecular weight heparin or direct factor
Xa inhibitors, unless such therapies are prohibited by drug-specific ineligibility
criteria.
- Patients with known active progressive brain metastases. Patients with previously
treated brain metastases are eligible, provided that the patient has not experienced a
seizure or had a clinically significant change in neurological status within one month
prior to screening. All patients with previously treated brain metastases must be
stable (clinically and radiologically) for at least one month after completion of
treatment and either off steroid treatment or only taking physiological doses of
steroids prior to the screening step.
- Patients with clinically significant pre-existing cardiac conditions, including
uncontrolled 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 three
months prior to the screening step.
- Patients with acute gastrointestinal bleeding within one month prior to the screening
step.
- Patients with any other clinically significant medical condition which, in the opinion
of the treating physician, makes it undesirable for the patient to participate in the
study or which could jeopardize compliance with study requirements including, but not
limited to: ongoing or active infection, significant uncontrolled hypertension, or
severe psychiatric illness/social situations.
- Lactating and nursing women
- Patients who do not meet drug-specific eligibility requirements for the drug selected
by the treating physician.
