Rash & Diarrhea Prophylaxis With Capivasertib

NCT07426822 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000037614
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, multicenter, phase II clinical trial evaluating prophylactic strategies to mitigate common toxicities associated with capivasertib in combination with fulvestrant in participants with hormone receptor-positive (HR+), HER2-negative advanced breast cancer who are eligible for this treatment regimen.

Conditions

Metastatic HR+/HER2- Breast Cancer

Keywords

Rash; Diarrhea; Capivasertib

Outcome Measures

Primary Outcomes (2)

• Number of patients who experience grade 2 or greater diarrhea as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  The study aims to evaluate the effectiveness of prophylactic strategies to mitigate diarrhea in patients receiving capivasertib in combination with fulvestrant for hormone receptor-positive (HR+), HER2-negative advanced breast cancer. Toxicities will be graded on the following scale: grade 1 mild, grade 2 moderate, grade 3 severe, grade 4 life threatening/disabling and grade 5 death related to AE.

  At the eight-week mark from the commencement of the capivasertib treatment in the study

• Number of patients who experience grade 2 or greater rash as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  The study aims to evaluate the effectiveness of prophylactic strategies to mitigate rash in patients receiving capivasertib in combination with fulvestrant for hormone receptor-positive (HR+), HER2-negative advanced breast cancer. Toxicities will be graded on the following scale: grade 1 mild, grade 2 moderate, grade 3 severe, grade 4 life threatening/disabling and grade 5 death related to AE

  At the eight-week mark from the commencement of the capivasertib treatment in the study

Secondary Outcomes (8)

• Rate of Adherence to Capivasertib in Patients with Metastatic HR+/HER2- Breast Cancer

  From the start of treatment to the end of the treatment period, assessed up to 24 months.

• Average Duration of Capivasertib Treatment from Initial to Final Dose

  From the start of treatment to the end of the treatment period, assessed up to 24 months

• Rates of Hyperglycemia in patients with metastatic HR+/HER2- breast cancer

  From the start of treatment to the end of the treatment period, assessed up to 24 months

• Quality of Life as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

  At baseline, every 4 weeks during treatment, and every 12 weeks during follow-up, up to 24 months

• Average Number of Completed Cycles of Capivasertib Treatment

  From the start of treatment to the end of the treatment period, assessed up to 24 months

Study Arms (2)

Rash and diarrhea prophylaxis

EXPERIMENTAL

All participants will receive capivasertib + fulvestrant. Capivasertib will be administered at 400 mg orally, twice daily (BID), on 4-days-on/3-days-off schedule. Fulvestrant will be administered at 500 mg intramuscularly (IM) every 14 days for the first three injections, and every 28 days thereafter. Participants in this arm will take cetirizine 10 mg orally once daily, and loperamide 2 mg orally once daily on capivasertib dosing days, starting on Cycle 1 Day 1 and continued for the first eight weeks (each cycle = 28 days).

Drug: Capivasertib; Drug: Loperamide; Drug: Fulvestrant; Drug: Ceterizine

Rash prophylaxis

EXPERIMENTAL

All participants will receive capivasertib + fulvestrant. Capivasertib will be administered at 400 mg orally, twice daily (BID), on 4-days-on/3-days-off schedule. Fulvestrant will be administered at 500 mg intramuscularly (IM) every 14 days for the first three injections, and every 28 days thereafter. Participants will take cetirizine 10 mg orally once daily, starting on Cycle 1 Day 1 and continued for the first eight weeks (each cycle = 28 days).

Drug: Capivasertib; Drug: Fulvestrant; Drug: Ceterizine

Interventions

Capivasertib DRUG

400 mg orally, twice daily (BID), on 4-days-on/3-days-off schedule.

Rash and diarrhea prophylaxis; Rash prophylaxis

Loperamide DRUG

2 mg orally once daily on capivasertib dosing days

Rash and diarrhea prophylaxis

Fulvestrant DRUG

500 mg Administered intramuscularly every 14 days for the first three injections and every 28 days thereafter.

Rash and diarrhea prophylaxis; Rash prophylaxis

Ceterizine DRUG

10 mg orally once a day, starting on Cycle 1 Day 1 and continued for the first eight weeks (each cycle=28 days)

Rash and diarrhea prophylaxis; Rash prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the clinical study protocol.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• Participants must be aged ≥18 years at the time of signing the ICF.
• Adult females, pre- and/or post-menopausal, and adult males:
• \- Pre-menopausal (and peri-menopausal i.e., those that do not meet the criteria for post-menopausal defined below) women can be enrolled if amenable to treatment with an LHRH agonist. Participants are to have commenced concomitant treatment with LHRH agonist at least four weeks prior to Cycle 1, Day 1 and must be willing to continue it for the duration of the study.
• Post-menopausal women are defined as:
• Aged ≥60 years of age, OR
• Aged \<60 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments/chemotherapy/ovarian suppression/tamoxifen or similar. These 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, OR
• Documented irreversible bilateral oophorectomy.
• Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent.
• Participants with metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations, as confirmed by local or central testing of tumor tissue and/or circulating tumor DNA (ctDNA).
• Participants eligible for treatment with capivasertib and fulvestrant for metastatic breast cancer.
• ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks and life expectancy of ≥12 weeks.
• Adequate hematologic, coagulation, hepatic, and renal parameters.
• Participants must be able to swallow and retain oral medication.

You may not qualify if:

• A disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment (e.g., symptomatic visceral disease that is potentially life-threatening in the short-term)
• Malignancies other than breast cancer within five years prior to study treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma or Stage I endometrioid uterine cancer).
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment.
• Known abnormalities in coagulation such as bleeding diathesis, or treatment anticoagulants precluding intramuscular injections of fulvestrant or LHRH, if applicable.
• Prior exposure to any chemotherapy or anti-cancer agents other than those specified in the protocol (e.g. hormonal therapy such as LHRH agonists) without appropriate washout period before randomization/enrollment, for example, randomization within 3 half-lives of a small molecule anti-cancer agent, or within 4 weeks for any antibody-based anticancer agents.
• Concurrent use of herbal or natural products intended as treatment or prophylaxis for any type of cancer.
• Radiotherapy within 2 weeks prior to the first dose of study intervention
• Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
• Strong inhibitors of CYP3A4 or strong/moderate inducers of CYP3A4 within 2 weeks prior to the first dose of capivasertib (3 weeks for St John's wort), Note that adequate washout or dose reduction may be required for some CYP3A substrates with a narrow therapeutic window prior to initiating capivasertib dosing.
• Any concomitant medication that may interfere with fulvestrant, cetirizine, and loperamide safety and efficacy based on the prescribing information of fulvestrant, cetirizine, and loperamide and local clinical guidelines.
• Clinically significant abnormalities of glucose metabolism as defined by any of the following:
• Participants with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment.
• HbA1c ≥8.0% (63.9 mmol/mol).
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids within four weeks prior to study treatment initiation.
• Leptomeningeal metastases.

Sponsors & Collaborators

• Maryam Lustberg: lead
• AstraZeneca: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Exanthema; Diarrhea

Interventions

capivasertib; Loperamide; Fulvestrant; ceterizine hydrochloride

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 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

• Maryam Lustberg, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Kane

CONTACT

773-369-6904; Laura.Kane@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 23, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)