Trial Title:
Adaptive Therapy With Capecitabine for the Treatment of Metastatic Estrogen Receptor Positive, HER2 Negative Breast Cancer
NCT ID:
NCT06525766
Condition:
Anatomic Stage IV Breast Cancer AJCC v8
Estrogen-receptor-positive Breast Cancer
Metastatic HER2-Negative Breast Carcinoma
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Capecitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (capecitabine)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (capecitabine)
Other name:
Bone Scintigraphy
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Given PO
Arm group label:
Treatment (capecitabine)
Other name:
Ro 09-1978/000
Other name:
Xeloda
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (capecitabine)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (capecitabine)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (capecitabine)
Summary:
This phase II trial evaluates the effect of capecitabine on tumor response using imaging
and tumor markers to adjust dose (adaptive therapy) in patients with estrogen receptor
(ER) positive, HER2 negative breast cancer that has spread from where it first started to
other areas in the body (metastatic). Capecitabine is in a class of medications called
antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a
substance that kills tumor cells. Adaptive therapy with capecitabine based on tumor
burden response may slow or stop the growth of tumor cells in patients with metastatic ER
positive, HER2 negative breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate the feasibility of adaptive therapy (AT) in hormone receptor positive
metastatic breast cancer, defined as the number of patients who can achieve AT
modification for 2 or more cycles.
SECONDARY OBJECTIVES:
I. To evaluate time to progression in patients receiving capecitabine AT defined as the
interval between treatment start and tumor progression, or death in patients with no
evidence of disease progression.
II. Assess overall survival in patients receiving capecitabine as adaptive therapy.
III. Evaluate patient related outcomes by measuring quality of life and global health
status of patients on AT using the European Organization for Research and Treatment of
Cancer (EORTC) Quality of Life Core 30 questionnaire EORTC QLQ C-30.
IV. Evaluate adverse events secondary to capecitabine using Common Terminology Criteria
for Adverse Events (CTCAE) grading system version 5.0.
V. Assess feasibility and accuracy of radiologic 3 dimensional (3D) volumetric approach
in measuring target lesions.
EXPLORATORY OBJECTIVES:
I. Assess circulating tumor deoxyribonucleic acid (DNA) (ctDNA) as a low-cost alternative
to imaging for measuring tumor burden.
II. Identify gene signatures that could predict response and identify mechanisms of
resistance to capecitabine using next generation sequencing technology, including:
IIa. Whole exome DNA sequencing from ctDNA at baseline (day 0) and end of treatment; IIb.
Whole transcriptome ribonucleic acid (RNA) sequencing from ctDNA at and at baseline (day
0) and end of treatment.
III. ctDNA quantification is optional at day 1 (D-1).
OUTLINE:
INITIAL STANDARD PHASE: Patients receive standard dose of capecitabine orally (PO) twice
daily (BID) on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of
disease progression or unacceptable toxicity. Patients whose disease has responded or
remains stable after 2 cycles continue to the Adaptive Phase.
ADAPTIVE PHASE: Patients receive 50% reduced dose of capecitabine PO BID on days 1-14 of
each cycle. Patients undergo blood sample collection every cycle and computed tomography
(CT) every other cycle for disease response assessment. Patients whose disease burden
decreases < 10% on CT or blood begins receiving an additional 50% reduced dose of
capecitabine PO BID on days 1-14 of each cycle. Patients whose disease burden is stable
on CT or blood continue receiving initial Adaptive Phase dose of capecitabine PO BID on
days 1-14 of each cycle. Patients whose disease burden increases > 10% on CT or blood
begin receiving a 50% dose increase in capecitabine PO BID on days 1-14 of each cycle.
Cycles repeat every 21 days in the absence of disease progression or unacceptable
toxicity.
Additionally, patients undergo blood sample collection, CT or magnetic resonance imaging
(MRI), and bone scan if indicated on study.
After completion of study treatment, patients are followed up every 3 months for up to 3
years from time of registration.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥ 18 years
- Histological confirmation of estrogen-receptor positive (ER+), HER2-negative
overexpression or amplification negative as per American Society of Clinical
Oncology (ASCO)/College of American Pathologists (CAP) guidelines, metastatic breast
cancer
- Measurable disease. Bone only disease allowed if associated with soft tissue
component that is measurable by Response Evaluation Criteria is Solid Tumors
(RECIST) 1.1 criteria
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Hemoglobin ≥ 9.0 g/dL (obtained ≤ 14 days prior to registration), no transfusions
allowed ≤ 14 days prior to registration
- Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 14 days prior to
registration)
- Platelet count ≥ 100,000/mm^3 (obtained ≤ 14 days prior to registration)
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to
registration)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x
ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration)
- Prothrombin time (PT)/international normalized ratio (INR)/activated partial
thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant
therapy and INR or aPTT is within target range of therapy (obtained ≤ 14 days prior
to registration)
- Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula
(obtained ≤ 14 days prior to registration)
- Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for
persons of childbearing potential only. NOTE: If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required
- Provide written informed consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willingness to provide mandatory blood specimens for correlative research
- Ability to undergo re-staging CT scans as required by the protocol
- Willing to return to enrolling institution at the specified frequency for follow-up
(during the active monitoring phase of the study)
Exclusion Criteria:
- Prior chemotherapy or use of antibody drug conjugate in the metastatic setting
- Any of the following, because this study involves an agent that has known genotoxic,
mutagenic and teratogenic effects:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ adequate
contraception
- Any of the following prior therapies:
- Major surgery ≤ 3 weeks prior to registration
- Radiation therapy ≤ 2 weeks prior to registration
- Evidence of visceral crisis or impending cord compression
- Evidence of uncontrolled brain metastasis requiring whole brain irradiation or
intervention
- Uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection
- symptomatic congestive heart failure
- unstable angina pectoris
- uncontrolled cardiac arrhythmia
- chronic oxygen dependence
- respiratory failure
- or psychiatric illness/social situations that would limit compliance with study
requirements
- Receiving any other investigational agent which would be considered as a treatment
for the primary neoplasm
- Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Non-melanotic
skin cancer or carcinoma-in-situ of the cervix
- If there is a history of prior malignancy, they must not be receiving other cancer
specific treatment. Except for antiestrogen treatment (aromatase inhibitors or
selective estrogen modulators) for their cancer are permitted if they meet other
eligibility criteria. Denosumab and zoledronic acid, are permitted as established
adjunct therapies per guidelines
- History of myocardial infarction ≤ 6 months prior to registration, or congestive
heart failure requiring use of ongoing maintenance therapy for life-threatening
ventricular arrhythmias
- Patients known to have certain homozygous or compound heterozygous dihydropyrimidine
dehydrogenase (DPYD) variants that result in complete absence of deoxypyridinoline
(DPD) activity
- History of severe hypersensitivity reactions to fluorouracil or capecitabine
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Arizona
Address:
City:
Scottsdale
Zip:
85259
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Lida A. Mina, M.D.
Email:
Principal Investigator
Start date:
October 15, 2024
Completion date:
October 15, 2029
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06525766
https://www.mayo.edu/research/clinical-trials
