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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Treatment will be administered on an inpatient or outpatient basis based on the type of medication selected. The investigatory will administer the drug as directed in the FDA approved label.
Supportive care regimens will vary depending on the type of drug that will be administered at the treating investigator's discretion.
1\) Next Gen Sequencing report obtained as Standard of Care within the past 12 months of enrollment date will be used. If more than one report exists in this time period, the most recent report will be used.
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Progression Free Survival Ratio
Estimation of progression-free ratio defined as the duration of time from start of treatment to the time of progression divided by the duration of time from the last treatment received pre-trial to the time of progression on that treatment. The median progression-free ratio will be estimated with the range and a two-sided Wilcoxon Signed Rank test will be calculated to see if the progression free survival ratio is different from 1.0. This trial is powered to detect differences in the progression-free ratio for those with actionable mutations identified by NGS results and then treated with a targeted therapy. A hypothesized PFS ratio larger than 1.3 would suggest that the targeted therapy is doing better than the previous treatment received (not targeted), and we assume a null hypothesis PFS ratio of 1.0 (no difference).
Time frame: From the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years
Overall Survival
Overall survival will be displayed using Kaplan-Meier curves with median survival times and 95% confidence intervals.
Time frame: From the start of treatment to date of death or date of last contact, up to 2 years
Number of Participants With Adverse Events
Adverse events will be summarized in incidence tables by type for all patients who received at least one cycle of treatment.
Time frame: Up to 30 days after treatment ends, up to 33 months
Response Rate
Response rate will be estimated for all patients with corresponding 95% confidence intervals. Complete response is the disappearance of all target lesions and normalization of tumor marker level. Any pathological lymph nodes must have reduction in short axis to less than 10 mm. Partial response is at least 30% decrease in the sum of diameters of target lesions. Progressive disease is greater than 20% increase and a minimum 5 mm increase over the nadir. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Up to 30 days after treatment ends, up to 33 months
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