Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02276443 |
| Other study ID # |
2014-0185 |
| Secondary ID |
NCI-2015-0019120 |
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 9, 2015 |
| Est. completion date |
November 30, 2026 |
Study information
| Verified date |
January 2024 |
| Source |
M.D. Anderson Cancer Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This clinical trial assesses whether a newly designed algorithm which looks at the genomic
signature of each patient's tumor to predict their sensitivity to standard of care treatment
verses being placed on a personally designed treatment trial can improve the responses in
patients with newly diagnosed triple-negative breast cancer (TNBC). Testing the primary tumor
biopsy for certain proteins and monitoring the lymphocyte infiltration into the tumors may
help doctors determine the sub-type of TNBC, and direct treatments that may work well. It is
not yet known whether assigning treatment based on the patient's tumor classification will
improve how well the tumor responds.
Description:
PRIMARY OBJECTIVE:
I. To conduct a prospective single arm, non-randomized trial to determine the impact of
implementation of a research platform that includes diagnostic imaging to assess response to
the initial phase of neoadjuvant chemotherapy combined with subtyping of TNBC in order to
select the appropriate targeted therapy trial to complete neoadjuvant chemotherapy in
patients found to have chemo-insensitive disease by imaging.
SECONDARY OBJECTIVES:
I. Measured as defined by Standardized Definitions for Efficacy End Points (STEEP) criteria
using the following prioritization: distant recurrence free interval (DRFI), recurrence free
survival (RFS), distant relapse-free survival (DRFS), overall survival (OS), invasive disease
free survival (IDFS), disease free survival including ductal carcinoma in situ (DFS-DCIS).
II. Evaluate the rates of enrollment into clinical trials for patients identified as having
chemotherapy insensitive disease.
III. Evaluate the frequency of pathologic response rates (pCR, RCB I-III residual disease) in
patients identified as chemotherapy sensitive versus insensitive.
IV. Determine the estimates of DRFI, RFS, DRFS, IDFS and DFS-DCIS at 3 years, and OS at 5 and
10 years in all patients.
X. Determine the pathologic response based on molecular characterization. XI. Determine the
estimates of DRFI, RFS, DRFS, IDFS and DFS-DCIS at 3 years, and OS at 5 and 10 years.
XII. Subset analyses of pathologic response and 3-year DRFI, RFS, DRFS, IDFS, and DFS-DCIS.
XIII. Compare the results of pathologic node-negative status (sentinel and/or non-sentinel
nodes) after neoadjuvant chemotherapy according to a genomic predictor of nodal response to
NACT, in subsets defined by pre-treatment clinical nodal status.
EXPLORATORY OBJECTIVES:
I. Future re-analysis of residual samples using a customized genomic diagnostic platform
(integrated "prospective-retrospective" biomarker analysis) to predict chemotherapy
sensitivity.
II. Generation and subsequent molecular characterization of patient derived xenograph (PDX)
models.
III. Clinical diagnostic development studies using residual samples (fresh and/or
formalin-fixed) within the Clinical Laboratory Improvement Amendments (CLIA)-compliant
Molecular Diagnostics Laboratory, and patient derived xenographs (PDX) to formally evaluate
the clinical validity and utility of future clinical genomic diagnostic tests that would
predict both response, recurrence, and survival from the treatments used in this clinical
trial (correlative "retrospective-prospective" biomarker analyses).
IV. Correlative science studies to identify molecular therapeutic targets for
treatment-insensitive TNBC using residual samples and PDX models.
V. Correlation of tumor features or changes as measured by diagnostic imaging to determine
potential predictors of treatment response.
VI. Determine polymerase chain reaction (pCR) rates in a cohort of patients who undergo
surgical resection after achieving complete radiological response after 4 cycles of adjuvant
chemotherapy (AC).
OUTLINE: Patients are assigned to 1 of 3 arms.
ARM A: Patients undergo baseline molecular and immunohistochemistry (IHC) evaluation of their
tumor biopsy, and receive the results. Patients then receive standard anthracycline-based
chemotherapy and undergo standard ultrasound at baseline, after 2 cycles, after 4 cycles of
treatment, and after completion of treatment (before surgery). Patients and physicians are
notified of the results of the molecular evaluation. Patients may then choose to continue
with standard taxane +/- platinum-based chemotherapy or participate in an experimental
clinical trial designed to match the molecular profile and triple-negative subtype. Patients
with tumors predicted to be insensitive to chemotherapy are advised to participate in a
clinical trial treating their tumor subtype.
ARM B: Patients undergo baseline molecular and IHC evaluation of their tumor biopsy, and
receive the results. Patients then receive standard anthracycline-based chemotherapy and
undergo standard ultrasound at baseline, after 2 cycles, and after 4 cycles of treatment.
Patients and physicians are notified of the results of the molecular evaluation. Patients may
then choose to continue with standard taxane +/- platinum-based chemotherapy or participate
in an experimental clinical trial designed to match the molecular profile and triple-negative
subtype. Patients with tumors predicted to be insensitive to chemotherapy are advised to
participate in a clinical trial treating their tumor subtype.
ARM C: Patients undergo baseline molecular and IHC evaluation of their tumor biopsy, and
receive the results. Patients then receive standard anthracycline-based chemotherapy with
immunotherapy and undergo standard ultrasound at baseline, after 2 cycles, and after 4 cycles
of treatment. Patients and physicians are notified of the results of the molecular
evaluation. Patients may then choose to continue with standard taxane +/- platinum-based
chemotherapy or participate in an experimental clinical trial designed to match the molecular
profile and triple-negative subtype. Patients with tumors predicted to be insensitive to
chemotherapy are advised to participate in a clinical trial treating their tumor subtype.
After completion of study treatment, patients are followed up for up to 5 years.
