DNA-guided Second Line Adjuvant Therapy for High Residual Risk, Estrogen Receptor Positive, HER-2 Negative Breast Cancer (DARE)

NCT04567420 | Recruiting Phase 2 FDA Drug

• 1 other identifier: DARE
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 19

Brief Summary

A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for high Residual risk, Estrogen Receptor positive, HER-2 negative breast cancer (DARE)

Conditions

Breast Cancer

Keywords

ctDNA; breast cancer; high residual risk

Outcome Measures

Primary Outcomes (2)

• Surveillance/ctDNA screening Phase

  Primary objective of the ctDNA screening (surveillance) phase is to assess the incidence of ctDNA detection (i.e. ctDNA positivity) in patients with ER positive HER2- breast cancer who are receiving standard of care adjuvant endocrine therapy but remain high risk for recurrence.

  enrollment

• Therapeutic Phase

  Primary objective of the therapeutic randomized phase is to assess whether palbociclib plus fulvestrant improves relapse free survival compared to standard endocrine therapy in patients with ER positive HER2 negative breast cancer with detectable circulating tumor DNA during adjuvant endocrine therapy without clinical evidence of metastatic disease.

  through study completion, an average of 6 years

Secondary Outcomes (5)

• Secondary Objective 1: Feasibility- correlation between clinically apparent metastatic or local disease and positive ctDNA result.

  enrollment

• Secondary Objective 2: Efficacy- assess the ability of positive ctDNA results to predict clinical relapse.

  through study completion, an average of 6 years

• Secondary Objective 3: Efficacy- assess whether ctDNA clearance is associated with improved relapse free survival and overall survival.

  through study completion, an average of 6 years

• Secondary Objective 4: Efficacy- assess the efficacy of the combination arm, palbociclib plus fulvestrant compared to the control arm.

  through study completion, an average of 6 years

• Secondary Objective 5: Safety and Tolerability- number of participants with treatment-related adverse event as assed by CTCAE V5.0.

  through study completion, an average of 6 years

Study Arms (2)

Arm A

EXPERIMENTAL

Palbociclib/Fulvestrant Combination

Drug: Palbociclib; Drug: Fulvestrant

Arm B

ACTIVE COMPARATOR

Adjuvant Therapy

Drug: Adjuvant Therapy

Interventions

Palbociclib DRUG

4 week cycles

Also known as: IBRANCE

Arm A

Fulvestrant DRUG

4 week cycles

Also known as: Faslodex

Arm A

Adjuvant Therapy DRUG

Standard of Care

Also known as: Standard of Care

Arm B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• High risk for recurrence HER-2 negative, ER positive invasive breast cancer. For this study, ER positivity is defined as equal to or greater than 10% ER positivity by immunohistochemistry, regardless of progesterone receptor (PR) status. Patients who are PR positive but ER negative are not eligible.
• Patients may have completed adjuvant endocrine therapy and are within 7 years since the date of their definitive breast surgery, or may be currently taking an aromatase inhibitor, or tamoxifen, as adjuvant endocrine therapy and have completed at least 6 months (i.e. 24 weeks), but no more than 7 years of endocrine therapy. Prior CDK4/6 therapy in the adjuvant setting, including participation in the PALLAS and PENELOPE trials, is allowed if the last treatment was 12 or more months ago. Adjuvant bisphosphonate therapy is allowed
• High risk for recurrence is defined as any one of the following (these criteria apply equally to both patients who underwent surgery first and those who received neoadjuvant chemotherapy or endocrine therapy before surgery). (i) Four or more involved ipsilateral axillary lymph nodes or positive ipsilateral supraclavicular, or ipsilateral infraclavicular, or internal mammary lymph nodes at diagnosis or after preoperative systemic therapy, regardless of tumour size. Microscopic positive lymph node (i.e. \<2 mm tumor deposit) is not counted as positive for eligibility for patients who underwent surgery first without any preoperative systemic therapy. Microscopic positive lymph nodes (i.e. \<2 mm tumor deposit) are considered as positive nodes for eligibility for patients who received preoperative systemic therapy. (ii) Tumor size \>5 cm and at least one macroscopically positive lymph node (i.e. \>2 mm tumor deposit).
• (iii) Diagnosis of Inflammatory Breast Cancer.
• Formalin fixed paraffin embedded tissue from the primary breast cancer available to be sent to Natera to perform ctDNA testing.
• Signed and dated informed consent, including willingness to be randomized to standard of care versus fulvestrant + palbociclib.

You may not qualify if:

• Prior or current treatment with fulvestrant, or current treatment with a CDK4/6 inhibitor, or treatment in the prior 12 months.
• Patients cannot start participation in another therapeutic clinical trial for breast cancer during participation in this trial unless disease progression occurred, or patient withdrew consent for participation in the current trial.
• Patients with current or past invasive cancer, other than breast cancer are not eligible, except: Adequately treated basal or squamous cell carcinoma of the skin and cancer survivors of previously diagnosed invasive cancer, who were treated with a curative intent, have no evidence of disease recurrence for 5 years or more, and are considered low risk for future recurrence by the treating physician are also eligible.
• Patients with a second HER2 positive or triple negative synchronous breast cancer.
• ctDNA positivity by the Signatera assay, defined as 2 of the 16 cancer specific markers positive in plasma.
• Patients with positive Signatera results obtained in the context of commercial testing, outside of the screening phase of this trial, are also eligible for randomization if they meet other eligibility criteria.
• No evidence of metastatic disease on CT scan of the chest, abdomen and pelvis.
• If imaging, after review with a radiologist, is low probability for metastatic disease, patients may proceed to randomization.
• Patients with suspicious but inconclusive imaging results should undergo a diagnostic biopsy, if biopsy is negative patients are eligible for randomization.
• Patients with positive imaging that is conclusive of metastatic disease, or with biopsy proven metastatic disease, are not eligible for randomization.
• Pre-menopausal women and male patients must be willing to use an adequate method of contraception for the duration of trial treatment and for 4 additional weeks after completion of treatment in the control arm, and for 2 years after the last dose of fulvestrant, if randomized into the experimental arm Post- menopausal status is defined as:
• Documented bilateral oophorectomy, or
• Age ≥ 60 years, or
• Age \< 60 years and amenorrhoeic for ≥ 12 consecutive months and FSH and estradiol levels in the post-menopausal range according to the institutional reference range for post- menopausal.
• Adequate contraception is defined as:

Sponsors & Collaborators

• Criterium, Inc.: lead

Study Sites (19)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

COMPLETED

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Intermountain

Golden, Colorado, 80401, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Louisiana State University Health Sciences Center- New Orleans

New Orleans, Louisiana, 70112, United States

RECRUITING

Cancer Partners of Nebraska

Lincoln, Nebraska, 68516, United States

RECRUITING

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87131, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Stony Brook University Cancer Center

Stony Brook, New York, 11794, United States

RECRUITING

The Ohio State University Wexner Medical Center James Cancer Hospital

Columbus, Ohio, 43210, United States

RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

PRiSMs Group

Laredo, Texas, 78041, United States

RECRUITING

Virginia Cancer Institute

Richmond, Virginia, 23229, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Fulvestrant; Chemotherapy, Adjuvant; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Combined Modality Therapy; Therapeutics; Drug Therapy; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Lajos Pusztai, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bebi Yassin-Rajkumar, MSc

CONTACT

6138511370; byassin-rajkumar@criteriuminc.com

Julee Hartwell

CONTACT

607-651-6273; jhartwell@criteriuminc.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 28, 2020
• Study Start: February 9, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)