Adding Capivasertib to Standard Treatment in HR Positive, HER2 Negative Metastatic Breast Cancer Based on ctDNA Testing

NCT07802626 | Not Yet Recruiting Phase 3 DMC FDA Device

• 1 other identifier: 21CTP.BREAST01
• Study Type: interventional
• Target: 1,084
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to see if adding the investigational targeted drug capivasertib to standard endocrine therapy (hormone-blocking treatment) combined with a medicine that slows cancer cell growth can improve response to treatment for patients with metastatic breast cancer that's hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative.

Conditions

HR Positive/HER-2 Negative Breast Cancer

Keywords

Metastatic; Breast Cancer; Capivasertib; HR Positive, HER2 Negative

Outcome Measures

Primary Outcomes (1)

• PFS

  To evaluate progression-free survival (PFS) in participants with HR-positive and HER2 negative unresectable or metastatic breast cancer with detectable circulating tumor DNA (ctDNA) at baseline who do not achieve molecular response but show no evidence of progression per RECIST 1.1 after three cycles of standard of care (SOC) treatment with non-steroidal aromatase inhibitor (NSAI) + CDK4/6 inhibitor in Arms 2 and 3. PFS will be evaluated separately in participants randomized to NSAI + CDK4/6 inhibitor + capivasertib (Arm 2) and fulvestrant + CDK4/6 inhibitor + capivasertib (Arm 3) and compared to historical control.

  Up to 5 years after Step 1 Registration

Secondary Outcomes (14)

• Molecular Response

  Up to 15 weeks after Step 1 Registration

• Cohort A Overall Survival

  Up to 5 years after Step 1 Registration

• Cohort A Clinical Benefit Rate

  Up to 5 years after Step 1 Registration

• Cohort A Overall Response Rate

  Up to 5 years after Step 1 Registration

• Cohort A Toxicities

  Up to 5 years after Step 1 Registration

Study Arms (4)

Cohort A, Arm 1

ACTIVE COMPARATOR

Continue NSAI + CDK4/6i

Drug: NSAI + CDK4/6i; Diagnostic Test: Guardant Reveal

Cohort A, Arm 2

EXPERIMENTAL

NSAI + CDK4/6i + Capivasertib

Drug: NSAI + CDK4/6i + Capivasertib; Diagnostic Test: Guardant Reveal

Cohort A, Arm 3

EXPERIMENTAL

Fulvestrant + CDK4/6i + Capivasertib

Drug: Fulvestrant + CDK4/6i + Capivasertib; Diagnostic Test: Guardant Reveal

Cohort B, Arm 1

ACTIVE COMPARATOR

Continue NSAI + CDK4/6i

Drug: NSAI + CDK4/6i; Diagnostic Test: Guardant Reveal

Interventions

NSAI + CDK4/6i + Capivasertib DRUG

NSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles; Capivasertib: Dosed 4 days on and 3 days off weekly, every cycle

Also known as: Cohort A, Arm 2

Cohort A, Arm 2

Guardant Reveal DIAGNOSTIC_TEST

ctDNA Assay

Cohort A, Arm 1; Cohort A, Arm 2; Cohort A, Arm 3; Cohort B, Arm 1

NSAI + CDK4/6i DRUG

NSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles

Also known as: Cohort A, Arm 1

Cohort A, Arm 1

Fulvestrant + CDK4/6i + Capivasertib DRUG

NSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles Capivasertib: Dosed 4 days on and 3 days off weekly, every cycle Fulvestrant: Dosed days 1 and 15 of Cycle 1 and Day 1 of Cycles 2+

Also known as: Cohort A, Arm 3

Cohort A, Arm 3

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
• Participants must have evidence of either 1) measurable disease with or without non-measurable disease, or 2) non-measurable disease only, but the non-measurable disease must include bone metastases. Participants must have a CT scan or MRI of the chest and abdomen AND a whole-body bone scan within 28 days prior to registration. X-rays, scans, or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form.
• Note: Participants cannot have only non-measurable disease without bone involvement.
• Participants must have HER2-negative breast cancer, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+ (i.e. indeterminate), a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing (as per the ASCO-CAP guidelines).
• Participants' most recent tumor biopsy or surgical resection specimen must be either ER-positive, PgR-positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the ASCO-CAP guidelines).
• Female participants must be at post-menopausal status or be receiving ovarian ablation with a GnRH agonist such as goserelin. Pre-menopausal (and peri-menopausal, i.e. those that do not meet the criteria defined for post-menopausal below) women are eligible if amenable to treatment with an GnRH agonist. Male participants should also receive GnRH agonist. These participants must begin concomitant treatment with GnRH agonist at least 14 days prior to Cycle 1, Day 1 and must be willing to continue concomitant treatment for the duration of the study. Post-menopausal status is defined by any one of the following criteria: Prior bilateral oophorectomy, Age ≥60 years, or Age \<60 and amenorrhea for 12 months following cessation of all exogenous hormonal treatments/chemotherapy/ovarian suppression/tamoxifen or similar. Participants should also have serum estradiol and follicle stimulating hormone (FSH) levels confirmed as being within the standard laboratory reference range for post-menopausal females per local institution standards.
• Participants must be ≥ 18 years old at the time of registration.
• Participants must have Zubrod Performance Status of 0 or 1.
• Participants must have a complete medical history and physical exam within 28 days prior to registration.
• Participants must have adequate organ and marrow function within 28 days prior to registration.
• Participants must have a calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration. For creatinine clearance formula see the tools on the CRA Workbench https://txwb.crab.org/TXWB/Tools.aspx.
• Participants must be given the opportunity to participate in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) form.
• Participants must agree to have blood specimens submitted for ctDNA molecular response assessment.
• Participants must be offered the opportunity to participate in planned non-real time ctDNA analysis.

You may not qualify if:

• Participants must not have active central nervous system (CNS) disease or evidence of active leptomeningeal disease.
• Participants must not have had endocrine resistance as defined as breast cancer recurrence within 12 months of cessation of endocrine therapy in the adjuvant setting. Prior adjuvant CDK4/6 inhibitor use is allowed as long as participants did not have a recurrence within 12 months of completion of treatment with an adjuvant CDK4/6 inhibitor.
• Participants must not have initiated, but must be planning to initiate, NSAI + palbociclib or ribociclib as the initial therapy for unresectable or metastatic disease.
• Participants must not have received prior systemic therapy in the metastatic setting, including chemotherapy or hormone therapy. Prior exposure to any chemotherapy or anti-cancer agents including hormonal therapy in the (neo)adjuvant setting is allowed as long as appropriate washout period before randomization/enrollment is met.
• Participants must not be concurrently using hormone replacement therapy.
• Participants must not have received prior fulvestrant or PI3K/AKT inhibitor treatment.
• Participants must not have received strong inhibitors or potent inducers or substrates of CYP3A4 or substrates of CYP2D6 within 14 days (21 days for St. John's Wort) prior to registration.
• Participants must agree to not use herbal or natural products intended as treatment or prophylaxis for any type of cancer.
• Participants must not have radiotherapy within 14 days prior to the Step 1 registration.
• Participants must not have a major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 28 days prior to Step 1 registration or an anticipated need for major surgery during the study.
• Participants must not have any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration with the exception of alopecia, lymphocyte decrease, grade 2 lymphopenia and grade 2 prior chemotherapy-therapy related neuropathy.
• Participants must not have uncontrolled diabetes mellitus or risk for hyperglycemia within 28 days prior to registration. Participants must plan to have serum glucose performed prior to beginning Step 1 treatment.
• Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy at registration and have undetectable viral load on the most recent test results prior to registration. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count of \> 350, no history of AIDS-defining opportunistic infection within the past 12 months, and on anti HIV medications for at least 28 days.
• Note: Lower CD4+ count values are acceptable if clinically indicated and the participant has a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity within a given cancer.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results, if indicated.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• SWOG Clinical Trials Partnerships, LLC: collaborator
• AstraZeneca: collaborator
• Guardant Health, Inc.: collaborator

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Interventions

capivasertib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; 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

Study Officials

• Kevin Kalinsky, M.D.

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SWOG Clinical Trials Partnerships

CONTACT

210-614-8808; CTP@swog.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2026
• First Posted: September 3, 2026
• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): October 30, 2034
• Study Completion (Estimated): October 30, 2035
• Last Updated: September 3, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share