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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma; Multiple Myeloma; Solid Tumor; Malignant Neoplasm; Mutation Abnormality
• Intervention / Treatment: Drug: Investigational Agent; Other: Supportive Care Regimens; Diagnostic test: Next Gen Sequencing Report

Detailed Description

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
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Drug Administration Based on Next Gen Sequencing Report; Investigators will select the first drug listed in the tumor analysis report for the first mutation listed in the tumor analysis report. However, If the subject has a medical contraindication to the first listed drug (according to the drug label) or the first listed drug cannot be obtained for the patient, the study team will select the next drug presented by the tumor sequencing report. Patients receive targeted therapy based on next generation sequencing report. Cycles repeat every 2, 4, or 6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Investigational Agent; 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.; Other: Supportive Care Regimens; Supportive care regimens will vary depending on the type of drug that will be administered at the treating investigator's discretion.; Diagnostic test: Next Gen Sequencing Report; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival will be displayed using Kaplan-Meier curves with median survival times and 95% confidence intervals.	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.	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.	Up to 30 days after treatment ends, up to 33 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stefan Grant, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2020
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 1, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Neoplasms; Multiple Myeloma
• Other Study ID Numbers: IRB00061185; P30CA012197 (U.S. NIH Grant/Contract); WFBCCC 04519 (Other Identifier: IRB - Wake Forest University Health Science); NCI-2019-06802 (Other Identifier: Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No