Precision Medicine for Patients With Identified Actionable Mutations

NCT04111107 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00061185WFBCCC 04519P30CA012197NCI-2019-06802
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor; Lymphoma; Multiple Myeloma; Malignant Neoplasm; Mutation Abnormality

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival

  From the start of treatment to date of death or date of last contact, up to 2 years

• Number of Participants With Adverse Events

  Up to 30 days after treatment ends, up to 33 months

• Response Rate

  Up to 30 days after treatment ends, up to 33 months

Study Arms (1)

Drug Administration Based on Next Gen Sequencing Report

EXPERIMENTAL

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; Other: Supportive Care Regimens; Diagnostic Test: Next Gen Sequencing Report

Interventions

Investigational Agent DRUG

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.

Drug Administration Based on Next Gen Sequencing Report

Supportive Care Regimens OTHER

Supportive care regimens will vary depending on the type of drug that will be administered at the treating investigator's discretion.

Drug Administration Based on Next Gen Sequencing Report

Next Gen Sequencing Report DIAGNOSTIC_TEST

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.

Drug Administration Based on Next Gen Sequencing Report

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma; Neoplasms

Interventions

Drugs, Investigational

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Results Point of Contact

• Title: Stefan Grant, MD
• Organization: Tulane University

sgrant6@tulane.edu

504-988-5800

Study Officials

• Stefan Grant, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 1, 2019
• Study Start: April 22, 2020
• Primary Completion: December 9, 2022
• Study Completion: February 9, 2023
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)