Ductal Carcinoma in Situ
Conditions
Keywords
active surveillance, hormone therapy, endocrine therapy
Brief summary
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.
Detailed description
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.
Interventions
DRUGTamoxifen
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.
DRUGExemestane
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
DRUGLetrozole
For postmenopausal women: standard oral doses of AI of choice: letrozole 2.5 mg daily.
DRUGAnastrazole
For postmenopausal women: standard oral doses of AI of choice: anastrozole 1 mg daily.
DRUGTestosterone + Anastrazole
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.
DRUGElacestrant
Investigational drug. Both pre- and post- menopausal subjects. Elacestrant 400mg PO with food once daily up to 36 months.
DRUGZ-endoxifen
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.
Sponsors
QuantumLeap Healthcare Collaborative
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
RECAST-DCIS is an open-label, multi-site platform study designed to offer women with Ductal cell Carcinoma In Situ (DCIS) 6 months of neo-adjuvant exposure to endocrine therapy with the intent of determining their suitability for long-term active surveillance without surgery.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A. Female, at least 18 years old B. Previous diagnosis of HR+ DCIS (at least 50% ER or PR; biopsy will have been performed previously at diagnosis) with or without microinvasion C. Patients who have previously received endocrine therapy should have a washout period of 4-6 weeks prior to the screening MRI on the RECAST-DCIS trial D. Bilateral mammogram performed within up to 4 months (120 days) of the start of trial treatment may be used for screening evaluation E. MRI performed within up to 2 months (60 days) of the start of trial treatment for lesion evaluation F. CBC w/ diff, CMP, and Lipid Panel within normal limits within a year of the start of trial treatment. Abnormal labs to be repeated within 60 days prior to the start of trial treatment. Patients will be considered eligible for screening labs that are abnormal or out-of-range if the investigator has deemed the lab results not-clinically significant G. Negative urine or serum pregnancy test within 1 month of the start of trial treatment H. Controlled HIV positive patients are allowed as long as their current medication does not contraindicate the study's investigational agent I. Willingness and ability to provide tumor samples for research
Exclusion criteria
A. Pregnant or actively breastfeeding women B. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent based on review of the medical record and patient history C. Invasive carcinoma or identification of a mass on MRI that is subsequently biopsied and found to be invasive cancer D. Co-enrollment in clinical trials of pharmacologic agents requiring an IND E. Ongoing treatment for DCIS other than what is specified in this protocol F. Uncontrolled intercurrent illness, including psychiatric conditions, that would limit compliance with study requirements G. Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of investigational agent and/or tamoxifen. Active inflammatory bowel disease or chronic diarrhea, known active hepatitis A/B/C\*, hepatic cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection or banding procedures \*Active hepatitis, defined as: A (positive HA antigen or positive IgM); B (either positive HBs antigen or positive hepatitis B viral DNA test above the lower limit of detection of the assay); C (positive hepatitis C antibody result, and quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay) H. Participants who are unable to swallow normally or unable to take tablets and capsules. Predictable poor compliance with oral treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients remaining on active surveillance at 7 months | 7 months | Fraction of patients remaining on active surveillance at 7 months compared to control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 months | 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) |
| 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 | 3 months | 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) |
| Associate rate of progression to Invasive Ductal Carcinoma (IDC) with risk categorization after 6 months of treatment at 3 years | 3 years | Correlation of low-risk categorization at 6 months with subsequent rate of Invasive Ductal Cell Carcinoma progression at 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 | 6 months | 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) |
| 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) | 6 months | 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 |
| To determine whether neoadjuvant endocrine therapy decreases automated background parenchymal enhancement (BPE and automated MRI density compared to Ai and Tamoxifen | 6 months | % with contralateral reduction in qualitative and automated BPE and % reduction in contralateral breast density |
| Determine adherence to active surveillance protocol | 5 years | 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. |
| Change in artificial intelligence predicted risk based on mammography | 5 years | Correlation of BPE change with agent and compare to quantitative imaging density |
Countries
United States
Contacts
CONTACTKim Nelson, RN
CONTACTTammy Neseth, MA, CCRP
PRINCIPAL_INVESTIGATORLaura Esserman, MD, MBA
University of California, San Fancisco - Department of Surgery
PRINCIPAL_INVESTIGATOR(Co-PI) Kelly Hewitt, MD, FACS
Huntsman Cancer Institute at the University of Utah
Outcome results
None listed