DCIS: RECAST Trial Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment

Registration Number
NCT06075953
Lead Sponsor
QuantumLeap Healthcare Collaborative
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.
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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 agg...

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
400
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
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
chemoprevention therapy per investigator choiceAnastrazolea. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. for postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) or standard dose (20 mg) of tamoxifen There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.
Testosterone + Anastrazole (T+Ai)Testosterone + AnastrazoleWhite solid pellet for subcutaneous insertion consisting of 100mg Testosterone and 4mg Anastrazole, an aromatase inhibitor. A cylindrical pellet (4.5mm diameter, 6.35mm diameter) is inserted subcutaneously in the upper outer gluteal region or iliac fossa every 3 months, with treatment up to 36 months. There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.
EndoxifenZ-endoxifen(Z)-endoxifen is the most active metabolite of the selective estrogen receptor modulator (SERM), tamoxifen. Standard dose: 10mg PO delayed release capsule of z-endoxifen once daily for treatment up to 36 months. same time with a glass of water either 1 hour before a meal or 2 hours after a meal and should not take with alcohol. For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed for an additional 5 years.
chemoprevention therapy per investigator choiceTamoxifena. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. for postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) or standard dose (20 mg) of tamoxifen There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.
chemoprevention therapy per investigator choiceLetrozolea. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. for postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) or standard dose (20 mg) of tamoxifen There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.
chemoprevention therapy per investigator choiceExemestanea. For premenopausal women: 20 mg or 5 mg tamoxifen orally b. for postmenopausal women: standard oral doses of AI of choice: exemestane 25 mg daily, letrozole 2.5 mg daily, or anastrozole 1 mg daily; or reduced exemestane dosing: 25 mg 3 times per week orally i. For postmenopausal women who are not tolerating an AI, low dose (5 mg) or standard dose (20 mg) of tamoxifen There is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants may continue treatment for up to 5 years.
ElacestrantElacestrantSelective estrogen receptor degrader, Standard dose: 400mg PO with food once daily for treatment up to 36 months. Dose reduction of Elacestrant by up to 2 dose levels permitted depending on toxicity; 400 mg to 300 mg then 300 mg to 200 mg Participants requiring more than 2 dose reductions must discontinue treatment For patients on this arm there is active follow up with MRI at baseline, 3 months, 6 months after treatment initiation, and every 6 months alternating MRI and mammogram for up to 5 years. Participants are followed by for an additional 5 years.
Primary Outcome Measures
NameTimeMethod
Patients remaining on active surveillance at 7 months7 months

Fraction of patients remaining on active surveillance at 7 months compared to control

Secondary Outcome Measures
NameTimeMethod
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 control3 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)

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 control6 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, a quality of life (QoL) assessment)

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 control6 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)

Associate rate of progression to Invasive Ductal Carcinoma (IDC) with risk categorization after 6 months of treatment at 3 years3 years

Correlation of low-risk categorization at 6 months with subsequent rate of Invasive Ductal Cell Carcinoma progression at 3 years

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 Tamoxifen6 months

% with contralateral reduction in qualitative and automated BPE and % reduction in contralateral breast density

Change in artificial intelligence predicted risk based on mammography5 years

Correlation of BPE change with agent and compare to quantitative imaging density

Determine adherence to active surveillance protocol5 years

Time to discontinuation of therapy (Tolerability of therapy) will be measured, and Adherence rates on each regimen, as well as PROP-R and FACT-ES score on each regimen will be measured. These assessments will be combined to evaluate efficacy and toxicity using a novel clinical benefit index.

Trial Locations

Locations (8)

Berkeley Outpatient Center

🇺🇸

Berkeley, California, United States

UCSF

🇺🇸

San Francisco, California, United States

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

🇺🇸

Winston-Salem, North Carolina, United States

Bryn Mawr Hospital

🇺🇸

Bryn Mawr, Pennsylvania, United States

Riddle Hospital

🇺🇸

Media, Pennsylvania, United States

Paoli Hospital

🇺🇸

Paoli, Pennsylvania, United States

Lankenau Medical Center

🇺🇸

Wynnewood, Pennsylvania, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

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