Patient case: 73-year-old female with breast cancer; genetic feature: CDKN2A

Clinical trial: TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

Summary: The purpose of the study is to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug.

Detailed description: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a non-randomized clinical trial that aims to describe the safety and efficacy of commercially available, targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has a potentially actionable genomic variant. TAPUR will study Food and Drug Administration (FDA)-approved targeted therapies that are contributed by collaborating pharmaceutical companies, catalogue the choice of molecular profiling test by clinical oncologists and develop hypotheses for additional clinical trials.

Eligibility: Inclusion Criteria:
  -  18 years of age or older
  -  Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of the treating physician, no such treatment is available or indicated
  -  Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG )criteria)
  -  Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/exclusion criteria specified in the protocol appendix for each agent will take precedence for this and all inclusion criteria:
  1. Absolute neutrophil count ≥ 1.5 x 106/µl
  2. Hemoglobin > 9.0 g/dl
  3. Platelets > 75,000/µl
  4. Total bilirubin < 2.0 mg/ dl
  5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases)
  6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
  -  Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor, Lugano criteria for non Hodgkin lymphoma or International Myeloma Working Group criteria for multiple myeloma), defined, per RECIST 1.1, as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not meet these definitions of measurable disease are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible
  -  Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified, College of American Pathologists (CAP) -accredited, New York State accredited (for labs offering services to residents of NY) laboratory that has registered the test with the National Institutes of Health (NIH) Genetic Test Registry or has established an integration with the TAPUR platform. The genomic or IHC test used to qualify a patient for participation in TAPUR may have been performed on any specimen of the patient's tumor 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 in a laboratory that meets the criteria described above.
  -  Ability to understand and the willingness to sign a written informed consent document
  -  Have a tumor genomic profile for which single agent treatment with one of the FDA approved targeted anti-cancer drugs included in this study has potential clinical benefit based on the criteria described in protocol
  -  For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome
  -  Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or if she is the partner of a male participant in this study and becomes pregnant while he is participating in this study, she should inform her or her partner's treating physician immediately as well as her obstetrician. Female study patients who become pregnant must immediately discontinue treatment with any study therapy. Male patients should avoid impregnating a female partner. Male study patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse
  Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have measurable and evaluable disease per RECIST v1.1
  Exclusion Criteria:
  -  Patients whose disease is not measurable or cannot be assessed by radiographic imaging or physical examination (e.g., elevated serum tumor marker only) are not eligible
  -  Patients with primary brain tumors are excluded. Patients with known progressive brain metastases determined by serial imaging or declining neurologic function in the opinion of the treating physician are not eligible. 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 the 3 months prior to registration. All patients with previously treated brain metastases must be clinically stable for at least 1 month after completion of treatment and off steroid treatment for one month prior to study enrollment.
  Note: there are additional exclusion criteria that may apply

Relevance to patient case: not relevant