Trial Title:
Liquid Biopsy-informed Precision Oncology Study to Evaluate Utility of Plasma Genomic Profiling for Therapy Selection
NCT ID:
NCT05585684
Condition:
Solid Tumor
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Other
Intervention name:
Non-invasive Comprehensive Genomic Profiling for Cancer Treatment Selection
Description:
Use of liquid biopsy to evaluate the clinical utility of non-invasive comprehensive
genomic profiling for cancer treatment selection.
Arm group label:
Oncology Patients
Summary:
Overall, this project has three main goals: first, to ascertain the feasibility of the
approach and identify whether liquid biopsies can detect actionable mutations that can be
utilized to generate precision oncology treatment recommendations. Second, the
investigators will investigate whether enacting upon MTB recommendations would improve
outcomes in terms of progression-free and overall survival. Third, the investigators aim
to determine if molecular profiling via serial plasma tests after initiation of
chemotherapy or other targeted treatment is sufficient to determine whether or not a
patient is responding to therapy.
Detailed description:
1. Quality assurance plan that addresses data validation and registry procedures,
including any plans for site monitoring and auditing.
All information will be collected on study-specific case report forms (CRFs) hosted
in Redcap and/or directly entered into a study database. The following measures will
be taken to protect patient information:
- The database will be password protected; only authorized staff may enter and
view project data.
- Passwords and system IDs will not be shared.
- Physical security of the workstations/files will be maintained. Workstations
with the database open will not be left unattended.
- Staff will be trained on the data entry system and on security procedures.
- The study data will be reviewed/monitored by the Sidney Kimmel Comprehensive
Cancer Center Clinical Research Office and the Cancer Center Safety committee.
2. Data checks to compare data entered into the registry against predefined rules for
range or consistency with other data fields in the registry.
Data checks will be performed per SKCCC SOP DM-01-04 CRF Documentation Standards.
Case Report Form (CRF): A printed, optical, or electronic document designed to
record all of the protocol-required information to be reported to the sponsor on
each trial subject. ICH GCP 1.11 Source Documents: Original documents, data, and
records (e.g., hospital records, clinical and office charts, laboratory notes,
memoranda, subjects' diaries or evaluation checklists, pharmacy dispensing records,
recorded data from automated instruments, copies or transcriptions certified after
verification as being accurate and complete, microfiches, photographic negatives,
microfilm or magnetic media, x-rays, subject files, and records kept at the
pharmacy, at the laboratories, and at the medicotechnical departments involved in
the clinical trial). ICH GCP 1.52
3. Source data verification to assess the accuracy, completeness, or representativeness
of registry data by comparing the data to external data sources (for example,
medical records, paper or electronic case report forms, or interactive voice
response systems).
All study data will be reviewed for completeness and accuracy by the Protocol Chair
who will ensure the completeness and accuracy of the data generated. The designated
research coordinator(s) participating in this project will collect clinical
information associated with each participant. Such data could include, but is not
limited to: medical record number, age, sex, treatment history, circulating tumor
markers, tumor size, tumor grade, tumor receptor status, pathology report, smoking
history, hormonal history, concomitant medications, and parity. Such information
will be retrieved from existing clinical databases/EMR (e.g., EPIC) and patient
questionnaire information, and may also include electronic scheduling and
prescription systems.
Follow-up information will be collected by review of the medical records. In
addition, participants may be reached by phone to help with any questions or
clarifications, or additional follow-up requirements.
4. Data dictionary that contains detailed descriptions of each variable used by the
registry, including the source of the variable, coding information if used (for
example, World Health Organization Drug Dictionary, MedDRA), and normal ranges if
relevant.
Source for data dictionary is included in Botsis et al., JCO CCI, 2023, in press.
5. Standard Operating Procedures to address registry operations and analysis
activities, such as patient recruitment, data collection, data management, data
analysis, reporting for adverse events, and change management.
These activities will be carried out in compliance with the study protocol and Good
Clinical Practice principles. Information regarding study conduct and progress will
be reported to our local Institutional Review Board (IRB) per current institutional
standards. The study will undergo routine annual review as per current institutional
standards.
6. Sample size assessment to specify the number of participants or participant years
necessary to demonstrate an effect.
We will recruit 150 patients with solid tumors including non-adenocarcinoma NSCLC,
small-cell lung cancer, neuroendocrine lung cancer, mesothelioma, esophageal cancer,
breast cancer and head and neck cancer. Based on the liquid biopsy assay's
analytical performance we expect to detect tumor-specific mutations in >85% of the
individuals. We expect to complete the accrual in 1.5 years. The analysis is
primarily descriptive for this feasibility study. A sample size of 150 patients will
provide reasonable confidence around the observed estimate of proportions, e.g.
percent of patients with variants of clinical significance. The width of 95%
confidence interval will be narrower than 16.5%.
7. Plan for missing data to address situations where variables are reported as missing,
unavailable, non-reported, uninterpretable, or considered missing because of data
inconsistency or out-of-range results.
Missing data will be excluded from downstream analyses.
8. Statistical analysis plan describing the analytical principles and statistical
techniques to be employed in order to address the primary and secondary objectives,
as specified in the study protocol or plan.
1. Analysis of Primary Objectives:
The primary objectives are to determine the number and prevalence of variants
with clinical significance across different levels of evidence (stratified by
gene and alteration type), as described above and to determine the percentage
of patients with an MTB treatment recommendation accordingly. Descriptive
analysis will be performed to estimate the percentage of patients that harbor
variants with clinical significance detected in ctDNA samples, along with 95%
confidence intervals. The percentage of patients with an MTB treatment
recommendation tailored to an actionable alteration according to the mutation
profiles detected by liquid biopsies, and percentage of patients treated
according to MTB recommendation will be estimated. The days from collection of
liquid biopsies to MTB recommendation, and days from MTB recommendation to
treatment initiation will be summarized by mean, median, standard deviation and
range. We plan to summarize the data after every 30 patients.
2. Analysis of Secondary Objectives:
Time to subsequent cancer therapy is the time from initiation of treatment to the start
of next cancer therapy according to treating physician's decision. Progression-free
survival (PFS) is the time from initiation of therapy to radiographic progression per
RECIST, clinical progression or worsening disease per treating physician's assessment.
Overall survival (OS) is the time from initiation of therapy to death due to any cause.
PFS and OS will be characteristics by Kaplan-Meier method, among patients who do and do
not have an MTB recommendation, and for patients who do and do not receive recommended
treatment.
Descriptive analysis will be performed to report the frequency of MTB-based treatment
recommendations by therapeutic class (standard of care, clinical trial, off-label use),
and the deviations from treatment recommendations and reasons (clinical deterioration,
other protocol, patient ineligible, off-label treatment unavailable, clinical trial not
feasible (e.g. physical distance), clinical trial not recruiting, physician's decision,
patient's choice, etc.) The concordance of detected alterations obtained through liquid
biopsy analyses at baseline compared to time-matched or archival tissue specimens will be
summarized and quantified using Kappa statistics.
Descriptive analyses will also be performed to determine the cell-free DNA yield and
ctDNA amount by tumor type obtained through liquid biopsy analyses. Additionally, the
assay success rate by tumor type and by pre-analytical variables will be performed across
minimum technical data elements, including:
- Blood collection tube type
- Sample composition
- Shipping temperature
- Blood fractionalization method
- Time to fractionation
- Analyte isolation method
- Time to freezer
- Storage temperature
- Concentration: cellular concentration or molecular concentration
- Assay method
- Time to assay
Criteria for eligibility:
Study pop:
Patients with solid tumors, including esophageal cancer, non-adenocarcinoma NSCLC,
small-cell lung cancer, head & neck cancer, mesothelioma, breast cancer and lung
neuroendocrine cancer.
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- ECOG performance status of 0-1.
- Patients with solid tumors, including esophageal cancer, non-adenocarcinoma NSCLC,
small-cell lung cancer, head & neck cancer, mesothelioma, breast cancer and lung
neuroendocrine cancer.
- Patients who can provide whole blood collection to meet minimum of 20-30ml of blood
at baseline, within 1-3 weeks from treatment initiation, at first radiographic
imaging and at progression. Acquisition of an archival or time-matched tumor tissue
specimen which meets the minimum sample input requirements (at least 20% tumor
content and 100 ng) is preferred but not required.
- Patients with metastatic disease will have progressed on the most recent treatment
prior to enrollment. Patient can also be enrolled if their oncologist believes
progression is imminent and test results would be used to inform next line of
therapy. Patients considered for first-line SOC therapeutic options may be enrolled
if the clinical efficacy of these therapies is not encouraging.
- Patients must have disease evaluable for progression assessment; measurable disease
is not required to participate in the study.
- Able to voluntarily provide informed consent.
Exclusion Criteria:
- Women who are known to be pregnant
- History of another primary malignancy in the last 5 years prior to registration
unless approved by the Protocol Chair/designee. Patients with prior history of in
situ cancer or basal or localized squamous cell skin cancer are eligible.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Locations:
Facility:
Name:
Johns Hopkins University
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Valsamo Anagnostou, MD, PhD
Phone:
410-614-8948
Email:
vanagno@jhmi.edu
Contact backup:
Last name:
Peggy Fitzpatrick, RN
Phone:
410-550-5848
Email:
mfitzpa7@jhmi.edu
Start date:
January 27, 2023
Completion date:
September 2025
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Collaborator:
Agency:
Personal Genome Diagnostics
Agency class:
Other
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05585684
