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

Ductal Carcinoma in Situ Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06075953
• Other study ID #: RECAST-DCIS
• Status: Recruiting
• Phase: Phase 2
• Start date: February 14, 2024
• Est. completion date: November 2033

Study information

• Verified date: January 2024
• Source: QuantumLeap Healthcare Collaborative
• Contact: Ami Okada, PhD MBA
• Phone: +1 (415)-610-7011
• Email: a.okada[@]quantumleaphealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: November 2033
• Est. primary completion date: November 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating
• Ductal Carcinoma in Situ

Intervention

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
• 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
• Letrozole
for postmenopausal women: standard oral doses of AI of choice: letrozole 2.5 mg daily,
• Anastrazole
for postmenopausal women: standard oral doses of AI of choice: anastrozole 1 mg daily;
• 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.
• Elacestrant
Investigational drug. Both pre- and post- menopausal subjects. Elacestrant 400mg PO with food once daily up to 36 months.
• 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.

Locations

Country	Name	City	State
United States	Berkeley Outpatient Center	Berkeley	California
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Riddle Hospital	Media	Pennsylvania
United States	Paoli Hospital	Paoli	Pennsylvania
United States	UCSF	San Francisco	California
United States	Atrium Health Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
QuantumLeap Healthcare Collaborative

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	Patients remaining on active surveillance at 7 months	Fraction of patients remaining on active surveillance at 7 months compared to control	7 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in artificial intelligence predicted risk based on mammography	Correlation of BPE change with agent and compare to quantitative imaging density	5 years