Clinical trial NCT06075953: DCIS: RECAST Trial Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment
Official title: DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ductal Carcinoma in Situ
Keywords: active surveillance
hormone therapy
endocrine therapy
Lead sponsor: QuantumLeap Healthcare Collaborative
Sponsor class: OTHER
First posted: 2023-10-10
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Female, at least 18 years old
* previous diagnosis of Hormone Receptor positive (HR+) DCIS (at least 50% ER or PR and 2+; biopsy will have been performed previously at diagnosis) with or without microinvasion
* Informed consent provided by the patient
* Willingness and ability to provide tumor samples for research

Exclusion Criteria:

* Pregnant or actively breastfeeding women (must be documented by a pregnancy test during screening)
* 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.
* Invasive carcinoma or identification of a mass on MRI that is subsequently biopsied and found to be invasive cancer
* Co-enrollment in clinical trials of pharmacologic agents requiring an Investigational new Drug Appilcation (IND)
* Ongoing treatment for DCIS other than what is specified in this protocol
* Uncontrolled intercurrent illness, including psychiatric conditions, that would limit compliance with study requirements.
* Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of investigational agent and/or tamoxifen. Participants unable to swallow normally or unable to take tablets and capsules. Predictable poor compliance to oral treatment. 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.

Primary outcomes:
measure: Patients remaining on active surveillance at 7 months
timeFrame: 7 months
Secondary outcomes:
measure: 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
timeFrame: 6 months
measure: 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
timeFrame: 3 months
measure: Associate rate of progression to Invasive Ductal Carcinoma (IDC) with risk categorization after 6 months of treatment at 3 years
timeFrame: 3 years
measure: 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 composite score compared to control
timeFrame: 6 months
measure: 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)
timeFrame: 6 months
measure: To determine whether neoadjuvant endocrine therapy decreases automated background parenchymal enhancement (BPE and automated MRI density compared to Ai and Tamoxifen
timeFrame: 6 months
measure: Determine adherence to active surveillance protocol
timeFrame: 5 years
measure: Change in artificial intelligence predicted risk based on mammography
timeFrame: 5 years
Other outcomes:
measure: Assess Germ Line polygenic risk: assess correlation of detectable mutations with endocrine response and qualification for active surveillance at 7 months
timeFrame: 7 months
measure: To evaluate outcomes stratified by immune and molecular subtype based upon multiplex immuno histochemistry (IHC) clustering analysis, and RPS expression array profiling
timeFrame: 7 months
Locations:
city: Berkeley
country: United States
facility: Berkeley Outpatient Center
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New York
country: United States
facility: Mount Sinai Union Square
state: New York
city: New York
country: United States
facility: Mount Sinai Chelsea
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
References: