Precision Medicine for Patients With Identified Actionable Mutations

Phase 2

Terminated

• Conditions: Solid Tumor; Lymphoma; Multiple Myeloma; Malignant Neoplasm; Mutation Abnormality
• Interventions: Drug: Investigational Agent; Other: Supportive Care Regimens; Diagnostic Test: Next Gen Sequencing Report

• Registration Number: NCT04111107
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-09-27
• Study First Submitted QC: 2019-09-30
• Study First Posted: 2019-10-01
• Study Start: 2020-04-22
• Primary Completion: 2022-12-09
• Study Completion: 2023-02-09
• Results First Submitted: 2024-05-20
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-11
• Last Update Submitted: 2024-06-11
• Results First Posted: 2024-07-03
• Last Update Posted: 2024-07-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug Administration Based on Next Gen Sequencing Report	Investigational Agent	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 Administration Based on Next Gen Sequencing Report	Supportive Care Regimens	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 Administration Based on Next Gen Sequencing Report	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival Ratio	From the start of treatment to the time of progression, death, or date of last contact, assessed up to 2 years	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).

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From the start of treatment to date of death or date of last contact, up to 2 years	Overall survival will be displayed using Kaplan-Meier curves with median survival times and 95% confidence intervals.
Number of Participants With Adverse Events	Up to 30 days after treatment ends, up to 33 months	Adverse events will be summarized in incidence tables by type for all patients who received at least one cycle of treatment.
Response Rate	Up to 30 days after treatment ends, up to 33 months	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.

Trial Locations

Locations (1)

Wake Forest Baptist Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States