Circulating Tumor DNA

Official title

A Single Arm Phase II Trial of Circulating Tumor DNA-guided Adjuvant Therapy With Elacestrant in Adults With Hormone Receptor Positive HER2 Negative Breast Cancers at Risk for Late Recurrence (CATE)

Overview

This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial. Our trial will proceed in three separate phases: screening, treatment, and follow-up.

Detailed description

This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial. Patients with ER+ breast cancer anatomic stage IIB or III at diagnosis who are at least five years from diagnosis and have completed intended course of adjuvant endocrine therapy and are currently off endocrine therapy will be screened with ctDNA testing. Patients who test positive for ctDNA during the screening phase will receive treatment with elacestrant for one year and continue ctDNA testing and imaging with CT scans every three months. During the follow-up period, patients in the study will continue to be ctDNA tested every six months and monitored for one year. If patients remain ctDNA positive at the completion of 12 months of study treatment, since they remain at increased risk of recurrence, they can choose to continue for an additional 12 months for a maximum of 24 months, they may also resume standard endocrine therapy or continue with standard of care surveillance during follow up.

Interventions

• Drug Elacestrant
  Administration of elacestrant will follow the FDA approved dose and schedule for patients with ER+ metastatic breast cancer. Elacestrant 345 mg will be administered orally once daily for 12 cycles or until disease progression or unacceptable toxicity. The pills shall be administered with food (to reduce nausea and vomiting) at approximately the same time each day, and the prescription will be provided with the standard "Swallow tablets whole; do not chew, crush, or split" warning label.

Primary outcome measures

• Assessing Elacestrant's Impact on ctDNA Clearance in ER+HER2- Breast Cancer Patients [Time frame: Every 3 months during the treatment phase and at 3-month intervals for 12 months following the end of treatment]
• Investigating Elacestrant's Effect on 18-Month Invasive Disease-Free Survival in ER+HER2- Breast Cancer Patients [Time frame: From the start of treatment through 18 months post-initiation of treatment]

Secondary outcome measures (8)

• Incidence of ctDNA Positivity in Screened ER+HER2- Breast Cancer Patients [Time frame: At baseline screening prior to treatment]
• Proportion of Patients with Metastatic Disease at First Positive ctDNA Result [Time frame: From baseline screening through the first positive ctDNA detection, up to 12 months]
• Time to Relapse Between First Positive ctDNA and Clinical Recurrence of Metastatic Disease [Time frame: From the first positive ctDNA detection through clinical recurrence, up to 24 months]
• Association of ctDNA Clearance with Recurrence-Free Survival and Overall Survival [Time frame: From baseline through 36 months post-treatment initiation]
• Safety, Tolerability, and Adherence to Elacestrant Treatment Protocol [Time frame: From baseline through the end of the treatment phase, up to 18 months]
• Patient-Reported Outcomes, Fear of Recurrence and Anxiety Levels During Elacestrant Treatment [Time frame: From baseline through the end of the treatment phase, assessed every 3 months up to 18 months]
• Assessing AmDTx-MBCS' Impact on Decreasing Fear of Recurrence Scores [Time frame: Participation in the application will be offered at the first screening visit. Fear of recurrence will be assessed from baseline through the end of the treatment phase, assessed every 3 months up to 18 months.]
• Diet and Physical Activity Levels in Breast Cancer Patients [Time frame: At the first screening visit only]

Eligibility criteria

Inclusion Criteria for Screening:

• Adults aged 18 years and older.
• Previous diagnosis of anatomic stage IIB or anatomic stage III histopathologically or cytologically confirmed ER+, HER2-, breast cancer per local laboratory as per ASCO/CAP guidelines. In the context of this trial, ER status will be considered positive if >10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry, with or without progesterone receptor positivity. Patients with PR positive but ER-negative are not eligible.
• Participants must have been diagnosed with ER+HER2- breast cancer at least five years ago and no more than 20 years ago and must have completed adjuvant endocrine therapy.
• Participants must be off endocrine therapy for at least four weeks prior to screening.

Exclusion Criteria for Screening:

• Known current metastatic disease.
• Known contraindication to receiving elacestrant as per FDA package insert.
• Current treatment with endocrine therapy.
• Prior treatment with elacestrant or other investigational SERDs.
• Current or past invasive cancer other than breast cancer, except:

• Adequately treated basal or squamous cell carcinoma of the skin.
• Cancer survivors of previously diagnosed invasive cancer who were treated with curative intent and have no evidence of disease recurrence for five years or more and are considered low risk for future recurrence by the treating physician.
• Patients in the screening phase, or in the randomized trial (treatment phase), cannot start receiving therapy on another therapeutic clinical trial.
• Current use of strong and moderate CYP3A4 inducers/inhibitors or other prohibited concomitant medication unless an acceptable substitute is available, and the prohibited medication is discontinued at least five half-lives prior to initiation of elacestrant.
• Participants who are pregnant.

Inclusion Criteria for Treatment:

• ctDNA positivity by NEXT Personal assay.
• No evidence of metastatic disease on staging scans.

a. If imaging, after review with a radiologist, is low probability for metastatic disease, patients may proceed with enrollment. Patients with suspicious but inconclusive imaging results should undergo a diagnostic biopsy; if biopsy is negative patients are eligible for enrollment. Patients with positive imaging that is conclusive of metastatic disease, or biopsy proven metastatic disease, are not eligible.

• At the time of informed consent signature for treatment, participants may be either postmenopausal, premenopausal, or perimenopausal.

a. Postmenopausal status is defined by: i. Age ≥60. ii. Age <60 and amenorrhea for 12 or more months (without an alternative cause) and FSH and estradiol level within postmenopausal range per local laboratory reference.

iii. Documentation of bilateral oophorectomy, at least one month before first dose of trial therapy.

b. Premenopausal and perimenopausal participants must be willing to concurrently receive an LHRH agonist, and the LHRH agonist must be initiated at least three to four weeks before the start of elacestrant and are planning to continue LHRH agonist treatment during treatment with elacestrant. This is based on the current FDA approval of elacestrant in the metastatic setting which is limited to postmenopausal participants.

c. Premenopausal or perimenopausal participants must be willing to use a highly effective method of contraception for the duration of trial treatment and for 120 days after the last dose of elacestrant OR if using barrier method of contraception must be willing to use a second form of contraception like occlusive cap with spermicidal foam / gel / film / cream / suppository.

i. Highly effective methods of contraception are non-hormonal (cooper) intrauterine device (IUD), surgical sterilization (bilateral tubal occlusion/ligation, partner who has had a vasectomy), and sexual abstinence.

• ECOG performance status of 0 or 1.
• Patient has adequate bone marrow and organ function, as defined by the following laboratory values:

• Absolute neutrophil count (ANC) >1.0 x 109/L.
• Platelets >100 x 109/L.
• Hemoglobin > 8.0 g/dL.
• Potassium, sodium, calcium, and magnesium CTCAE v5.0 grade <1.
• Cockcroft-Gault based creatinine clearance >50 mL/min.
• ALT and AST <3 x ULN and total serum bilirubin <1.5 x ULN.
• Hypercholesterolemia and hypertriglyceridemia CTCAE v5.0 grade <1.

Exclusion Criteria for Treatment:

• Any concurrent severe and uncontrolled medical condition that would, in the sponsor-investigator's opinion, cause unacceptable safety risks or compromise compliance with the protocol including but not limited to:
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral medication (uncontrolled Crohn's disease or ulcerative colitis, uncontrolled chronic nausea, vomiting, diarrhea, malabsorption, or small bowel resection).
• Females who are pregnant or breastfeeding.
• Moderate to severe liver impairment (Child-Pugh Class B and C).
• Hypercholesterolemia or hypertriglyceridemia > CTCAE v5.0 grade 1.
• Participants who are currently or are planning lactation during elacestrant treatment. Lactation during and at least one week following the last dose of elacestrant is not allowed

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Yale University — New Haven
• Lombardi Comprehensive Cancer Center at Georgetown University Medical Center — Washington D.C.
• Sidney Kimmel Comprehensive Cancer Center at John Hopkins — Baltimore
• Dana-Farber Cancer Institute — Boston
• Montefiore Einstein Comprehensive Cancer Center — The Bronx
• UPMC Hillman Cancer Center — Pittsburgh
• The University of Texas MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT06923527 · 2000039112

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗