Precision Medicine for Patients With Identified Actionable Mutations

Precision Medicine for Patients With Identified Actionable Mutations at Wake Forest Baptist Comprehensive Cancer Center (WFBCCC): A Pragmatic Trial-

The goal of the current pragmatic trial is to evaluate the impact of a simple method of selecting a treatment approach for identified mutations on participants' progression free survival (PFS). The study also intends to collect information on barriers that investigators encounter when prescribing treatment options using the Next Generation Sequencing (NGS) reports. Additionally, patients' quality of life will be measured before, after, and during treatment.

Patients will be followed until death for monitoring survival study endpoints.

Primary Objective:

• To estimate the progression-free ratio, as defined by the progression-free survival time on study treatment divided by the progression-free survival time on the last treatment received by patient, for an identified actionable mutation, who will be treated with an off-label treatment off label therapy based on a simplified selection methodology using the Next Generation Sequencing results.

Secondary Objectives:

• To estimate patient response rate on off-label treatments for actionable mutations based on Next Generation Sequencing results.
• To estimate overall survival (OS) for patients treated with off-label treatments for actionable mutations based on Next Generation Sequencing results.
• To describe the safety of using off-label or other experimental treatments for patients with actionable mutations based on Next Generation Sequencing results.

Exploratory Objectives:

• To describe health related quality of life in patients undergoing off-label treatment targeting genetic mutations, as measured by the PROMIS-29 Overall Health-Related Quality of Life, Including 4-Item Anxiety Subscale.
• Using the Satisfaction with Medical Decision Scale, to describe patient satisfaction with decision to pursue off-label treatment.
• To identify types of actionable mutations with available targeted treatment occurring in cancer patients.
• To characterize the historical treatment regimens for these patients relative to the targetable mutation.
• To describe patient clinical and demographic characteristics of those with actionable mutations based on Next Generation Sequencing results.
• To identify barriers to treatment based on Next Generation Sequencing results.

Inclusion Criteria:

• Cancer patients at Wake Forest Baptist Comprehensive Cancer Center and its satellites who have next generation DNA sequencing results on their tumor biopsy or surgically resected tissue and/or blood samples and/or consent to the Wake Forest Comprehensive Cancer Center Precision Oncology Registry to use their information for research.
• Actionable mutation (defined as a mutation or gene amplification for which an off-label therapy is identified on the patient's NGS report for which NCCN guidelines do not recommend a specific treatment in the particular disease or for which there is no documentation in the patient's medical record of clinical data demonstrating lack of activity with the targeting of the specific mutation or amplification in the patient's specific disease) uncovered by the genomic sequencing of a tumor or those that have undergone liquid biopsy assay of their tumor genomic, performed by Wake Forest or another and who are medically able to receive targeted therapy based on those results.
• Sequencing on a sample collected within 3 months prior to registration is strongly encouraged but must have been performed within the 12 months prior to registration.
• Patients must have progressed through at least two lines of treatment, or are not candidates for or unwilling to receive any standard therapies. Patients who have received treatment on the present protocol who have progression of disease may be recruited to the trial for treatment using another targeted therapy provided that they fulfill the other criteria for participation in the trial. If a patient discontinues treatment on this protocol they can be considered for further participation in this trial provided they meet all of the eligibility criteria and are eligible for re-registration and re-consent.
• Eastern Cooperative Oncology Group (ECOG) of less than or equal to 3
• Life expectancy of greater than 6 weeks
• The effects of the drugs used for cancer treatment on the developing human fetus are unknown. For this reason and because of the possibility that the agents are teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

• Patients who have had or will receive chemotherapy or radiotherapy to major bone marrow bearing sites within 2 weeks prior to receiving treatment on the study
• Patients who have not recovered from toxicity of prior treatment if such toxicity will preclude treatment with the proposed targeted agent.
• Patients may not be receiving any other investigational agents.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the targeted agent, breastfeeding should be discontinued if the mother is treated with the targeted agent.