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

DCIS: RECAST Trial -Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment: a Breast Cancer Prevention Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Ductal Carcinoma in Situ
• Intervention / Treatment: Drug: Tamoxifen; Drug: Exemestane; Drug: Letrozole; Drug: Anastrazole; Drug: Elacestrant; Drug: Z-endoxifen; Drug: Testosterone + Anastrazole

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria Pitsiouni, PhD; Phone Number: 172 (415) 651-8047; Email: m.pitsiouni@quantumleaphealth.org
• Study Contact Backup: Name: Ami Okada, PhD MBA; Phone Number: +1 (415)-610-7011; Email: a.okada@quantumleaphealth.org

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF
      • Contact: Cristian Maldonado-Rodas; Phone Number: 415-502-8545; Email: Cristian.MaldonadoRodas@ucsf.edu
      • Contact: Hannah Chay; Phone Number: 415-502-2841; Email: hannah.chay@ucsf.edu
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health Wake Forest Baptist Comprehensive Cancer Center
      • Principal Investigator: Marissa Howard-McNatt, MD
      • Contact: Sydney Sanders; Phone Number: 336-713-3155; Email: sysander@wakehealth.edu
      • Contact: Jonah Riley; Phone Number: (336) 713-9180; Email: jriley@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: chemoprevention therapy per investigator choice; a. 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.	Drug: Tamoxifen; For premenopausal women: 20 mg or 5 mg tamoxifen orally for postmenopausal women: For postmenopausal women who are not tolerating an AI, investigators can change them to the low dose (5 mg) or standard dose (20 mg) of tamoxifen; Drug: Exemestane; 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; Drug: Letrozole; for postmenopausal women: standard oral doses of AI of choice: letrozole 2.5 mg daily,; Drug: Anastrazole; for postmenopausal women: standard oral doses of AI of choice: anastrozole 1 mg daily;
Experimental: Elacestrant; Selective 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.	Drug: Elacestrant; Investigational drug. Both pre- and post- menopausal subjects. Elacestrant 400mg PO with food once daily up to 36 months.
Experimental: 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.	Drug: Z-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.
Experimental: Testosterone + Anastrazole (T+Ai); White 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.	Drug: Testosterone + 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.; Other Names: T+Ai

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients remaining on active surveillance at 7 months	Fraction of patients remaining on active surveillance at 7 months compared to control	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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	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 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, a quality of life (QoL) assessment)	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	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	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 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.	5 years
Change in artificial intelligence predicted risk based on mammography	Correlation of BPE change with agent and compare to quantitative imaging density	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Germ Line polygenic risk: assess correlation of detectable mutations with endocrine response and qualification for active surveillance at 7 months	evaluate influence of polygenic risk on endocrine response and suitability for Active Surveillance	7 months
To evaluate outcomes stratified by immune and molecular subtype based upon multiplex immuno histochemistry (IHC) clustering analysis, and RPS expression array profiling	Response stratified by multiplex immune staining for Human Epidermal growth factor receptor-2 (HER2) isoforms and Response Predictive Subtypes (RPS)	7 months

Collaborators and Investigators

• Sponsor: QuantumLeap Healthcare Collaborative

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2033

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: October 4, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: hormone therapy; active surveillance; endocrine therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Carcinoma in Situ; Carcinoma; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Androgens; Letrozole; Tamoxifen; Testosterone; Anastrozole; Exemestane
• Other Study ID Numbers: RECAST-DCIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No