The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with ductal cell carcinoma in situ (DCIS), an early stage of breast cancer, can be an effective management of the disease. Participants will be asked to receive control hormonal therapy or an investigational hormonal therapy treatment. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation participants will have the option to continue on the treatment. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to provide blood sample to understand their immune status, provide saliva sample for genetic testing, provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care.
The goal of this trial is to see if active surveillance monitoring and hormonal therapy in patients diagnosed with Ductal cell Carcinoma In Situ (DCIS), an early stage of breast cancer, can be an effective management of the disease. The current management of most patients with DCIS involves surgical intervention with or without radiation, similar to more aggressive breast cancers. These treatments can come with some significant health effects.The main question this study aims to answer is: to determine whether novel endocrine therapy increases the fraction of patients who will be suitable for long-term active surveillance. Participants will be asked to take one of three investigational study medication (z-Elacestrant, Testosterone + Anastrazole, or Endoxifen) or receive control hormonal therapy (Tamoxifen or an aromatase inhibitor), depending on the treatment to which they have been randomized. Participants will be asked to return for evaluation with MRI at three months and six months. Depending on the evaluation, participants will have the option to continue on the treatment, with follow up evaluations of Mammogram and MRI at 6 month intervals. If the evaluation suggests surgery is recommended, the participant will discontinue the study treatment and will undergo surgery. In addition to the treatment and MRI evaluation, participants will be asked to: * Provide blood sample to understand their immune status * Provide saliva sample for genetic testing * Provide the study with a portion of the tissue or slides generated from tissue removed during surgery performed as part of their standard of care. Participants will be followed annually for 10 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
For premenopausal women: 20 mg tamoxifen orally daily (standard dose) or 10 mg every other day (low dose). For postmenopausal women who are not tolerating an AI, investigators can change them to the low dose (10 mg every other day) or standard dose (20 mg) of tamoxifen.
For postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, or reduced exemestane dosing: 25 mg 3 times per week orally
For postmenopausal women: standard oral doses of AI of choice: letrozole 2.5 mg daily.
For postmenopausal women: standard oral doses of AI of choice: anastrozole 1 mg daily.
Investigational drug. Both pre- and post- menopausal subjects. 100mg testosterone in combination with 4mg anastrazole administered subcutaneously every 3 months for up to 3 years.
Investigational drug. Both pre- and post- menopausal subjects. Elacestrant 400mg PO with food once daily up to 36 months.
Investigational drug. Both pre- and post- menopausal subjects. (z)-endoxifen 10mg delayed release capsule 1 hour before a meal or 2 hours after a meal once daily for up to 36 months.
Berkeley Outpatient Center
Berkeley, California, United States
RECRUITINGCity of Hope -Duarte Cancer Center
Duarte, California, United States
RECRUITINGCity of Hope - Lennar Foundation Cancer Center
Irvine, California, United States
RECRUITINGUCLA
Los Angeles, California, United States
Patients remaining on active surveillance at 7 months
Fraction of patients remaining on active surveillance at 7 months compared to control
Time frame: 7 months
To determine whether novel endocrine therapy increases the fraction of patients who will be suitable for long-term active surveillance as measured by the fraction of patients deemed to be low-risk for invasive cancer at 6 months compared to control
Fraction of patients categorized as low risk by MRI after 6 months of treatment--Measured by cases demonstrating endocrine responsiveness (Determined based on lesion and background or lesion alone or lack of lesion and minimal background)
Time frame: 6 months
To determine whether novel endocrine therapy increases the fraction of patients who will be suitable for long-term active surveillance as measured by the fraction of patients deemed to be low-risk for invasive cancer at 3 months compared to control
Fraction of patients categorized as low risk by MRI after 3 months of treatment--Measured by cases demonstrating endocrine responsiveness (Determined based on lesion and background or lesion alone or lack of lesion and minimal background)
Time frame: 3 months
Associate rate of progression to Invasive Ductal Carcinoma (IDC) with risk categorization after 6 months of treatment at 3 years
Correlation of low-risk categorization at 6 months with subsequent rate of Invasive Ductal Cell Carcinoma progression at 3 years
Time frame: 3 years
To assess the QoL impact of novel endocrine therapy compared to tamoxifen or Aromatase inhibitor (Ai) at standard or low dose using PROMIS and the FACT-ES and FACT-GP5 composite score compared to control
Fraction of patients experiencing Minimum Important Difference in overall QOL measured by PROP-R statistics (PROMIS) and FACT-ES (functional assessment of cancer therapy- endocrine symptoms) and FACT-GP5, a quality of life (QoL) assessment)
Time frame: 6 months
For those with an identified lesion on MRI imaging, determine whether neoadjuvant endocrine therapy decreases lesion volume (qualitative, quantitative) and whether that corresponds to the biologic type of Ductal cell carcinoma In Situ (DCIS)
Rate of reduction in focal lesions (mass and non-mass enhancement (NME) at 6 months and Rate of reduction in focal lesions using automated Functional Tumor Volume
Time frame: 6 months
To determine whether neoadjuvant endocrine therapy decreases automated background parenchymal enhancement (BPE and automated MRI density compared to Ai and Tamoxifen
% with contralateral reduction in qualitative and automated BPE and % reduction in contralateral breast density
Time frame: 6 months
Determine adherence to active surveillance protocol
Time to discontinuation of therapy (Tolerability of therapy) will be measured, and Adherence rates on each regimen, as well as PROP-R, FACT-ES and FACT-GP5 score on each regimen will be measured. These assessments will be combined to evaluate efficacy and toxicity using a novel clinical benefit index.
Time frame: 5 years
Change in artificial intelligence predicted risk based on mammography
Correlation of BPE change with agent and compare to quantitative imaging density
Time frame: 5 years
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UCSF
San Francisco, California, United States
RECRUITINGCity of Hope
South Pasadena, California, United States
RECRUITINGJohn Muir Health
Walnut Creek, California, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGWinship Cancer Institute, Emory University
Atlanta, Georgia, United States
RECRUITINGUniversity of Chicago Medical Center
Chicago, Illinois, United States
RECRUITING...and 18 more locations