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Precision Medicine for Patients With Identified Actionable Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04111107
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : November 9, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Tracking Information
First Submitted Date  ICMJE September 27, 2019
First Posted Date  ICMJE October 1, 2019
Last Update Posted Date November 9, 2020
Actual Study Start Date  ICMJE April 22, 2020
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 8, 2019)
Progression Free Survival [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
Progression Free Survival [ Time Frame: 4 weeks ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
  • Overall Survival [ Time Frame: 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.
  • Incidence of Adverse Events [ Time Frame: Up to 30 days after treatment ends ]
    Adverse events will be summarized in incidence tables by type and grade severity for all patients and presented by type of treatment received.
  • Response Rate [ Time Frame: Up to 30 days after treatment ends ]
    Response rate will be estimated for all patients with corresponding 95% confidence intervals.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Quality of Life Using the Patient Reported Outcome Measurement Information System (PROMIS) 29 Survey [ Time Frame: Baseline up to 30 days after treatment ends ]
    The PROMIS-29 v 2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance). on symptom oriented domains of PROMIS-29 (anxiety, depression, fatigue, pain interference, and sleep disturbance), higher scores represent worse symptomatology. On the function oriented domains (physical functioning and social role) higher scores represent better functioning.
  • Overall Survival [ Time Frame: From the start of treatment to date of death or date of last contact, up to approximately 3 years ]
    Overall survival will be displaying using Kaplan-Meier curves with median survival times and 95% confidence intervals.
  • Incidence of Adverse Events [ Time Frame: Up to 30 days after treatment ends ]
    Adverse events will be summarized in incidence tables by type and grade severity for all patients and presented by type of treatment received.
  • Response Rate [ Time Frame: Up to 30 days after treatment ends ]
    Response rate will be estimated for all patients with corresponding 95% confidence intervals.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Precision Medicine for Patients With Identified Actionable Mutations
Official Title  ICMJE Precision Medicine for Patients With Identified Actionable Mutations at Wake Forest Baptist Comprehensive Cancer Center (WFBCCC): A Pragmatic Trial-
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Lymphoma
  • Multiple Myeloma
  • Malignant Neoplasm
  • Mutation Abnormality
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Drug: Investigational Agent
  • Other: Supportive Care Regimens
  • Diagnostic Test: Next Gen Sequencing Report
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 30, 2019)
337
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Coordinator 336-716-5440 rpetro@wakehealth.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04111107
Other Study ID Numbers  ICMJE IRB00061185
WFBCCC 04519 ( Other Identifier: IRB - Wake Forest University Health Science )
P30CA012197 ( U.S. NIH Grant/Contract )
NCI-2019-06802 ( Other Identifier: Clinical Trials Reporting Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Wake Forest University Health Sciences
Study Sponsor  ICMJE Wake Forest University Health Sciences
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Stefan Grant, MD Wake Forest University Health Sciences
PRS Account Wake Forest University Health Sciences
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP