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

QuantumLeap Healthcare Collaborative

Status and phase: Enrolling; Phase 2

Conditions: Ductal Carcinoma in Situ

Treatments: Drug: Tamoxifen; Drug: Testosterone + Anastrazole; Drug: Exemestane; Drug: Z-endoxifen; Drug: Elacestrant; Drug: Anastrazole; Drug: Letrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT06075953

RECAST-DCIS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 4 patient groups

chemoprevention therapy per investigator choice

Active Comparator group

Description:

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.

Treatment:

Drug: Letrozole

Drug: Anastrazole

Drug: Exemestane

Drug: Tamoxifen

Testosterone + Anastrazole (T+Ai)

Experimental group

Description:

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.

Treatment:

Drug: Testosterone + Anastrazole

Elacestrant

Experimental group

Description:

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.

Treatment:

Drug: Elacestrant

Endoxifen

Experimental group

Description:

(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.

Treatment:

Drug: Z-endoxifen