Rash & Diarrhea Prophylaxis With Capivasertib

Inclusion Criteria: 1. 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. 2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses. 3. Participants must be aged ≥18 years at the time of signing the ICF. 4. 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. 5. 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. 6. 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). 7. Participants eligible for treatment with capivasertib and fulvestrant for metastatic breast cancer. 8. ECOG performance status 0 or 1 with no deterioration over the previous 2 weeks and life expectancy of ≥12 weeks. 9. Adequate hematologic, coagulation, hepatic, and renal parameters. 10. Participants must be able to swallow and retain oral medication. 11. Participants must adhere to the following reproductive and contraceptive requirements: a. For participants of childbearing potential (POCBP): i. Participant of childbearing potential is defined as an individual who is premenopausal and capable of becoming pregnant, including those using contraception, those who are single, or those with partners who have had a vasectomy. ii. Participants must not be pregnant or breastfeeding. iii. A negative serum pregnancy test must be obtained at screening within 72 hours before the first dose of the study treatment, and participants must agree to further pregnancy tests throughout the study, if required. iv. Participants must use at least one highly effective method of contraception combined with a barrier method while on study treatment and for 1 years after the last dose of the study drug. v. Participants must not donate or freeze eggs for future use related to assisted reproduction while on study treatment and for 1 month after the last dose of the study drug. b. For participants with partners of childbearing potential: i. If a participant has a partner who could become pregnant, that partner must use a highly effective method of contraception combined with a barrier method while the participant is on study treatment and for 16 weeks after the last dose of the study drug, unless the participant is vasectomized. ii. Participants must not donate or freeze sperm for future use related to assisted reproduction while on study treatment and for 4 months after the last dose of the study drug. c. Highly effective methods of contraception include: i. Combined hormonal contraception (estrogen and progestogen) that inhibits ovulation (oral, intravaginal, or transdermal). ii. Progestogen-only hormonal contraception that inhibits ovulation (oral, injectable, or implantable). iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system. v. Bilateral tubal occlusion. vi. Sexual abstinence (the reliability of abstinence must be evaluated concerning the duration of the clinical study and the participant's lifestyle). vii. A vasectomized partner (provided the partner is the sole sexual partner of the POCBP study participant and that the vasectomized partner has received medical confirmation of the surgical success). d. Barrier methods are not considered highly effective and should not be used alone to meet study contraceptive requirements. However, they may be used in addition to a highly effective method for extra protection. These include: i. Male condom. ii. Female condom. iii. Cervical cap. iv. Diaphragm with spermicide. v. Contraceptive sponge with spermicide Exclusion Criteria: 1. 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) 2. 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). 3. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment. 4. Known abnormalities in coagulation such as bleeding diathesis, or treatment anticoagulants precluding intramuscular injections of fulvestrant or LHRH, if applicable. 5. 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. 6. Concurrent use of herbal or natural products intended as treatment or prophylaxis for any type of cancer. 7. Radiotherapy within 2 weeks prior to the first dose of study intervention 8. 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. 9. 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. 10. 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. 11. Clinically significant abnormalities of glucose metabolism as defined by any of the following: 1. Participants with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment. 2. HbA1c ≥8.0% (63.9 mmol/mol). 12. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids within four weeks prior to study treatment initiation. 13. Leptomeningeal metastases. 14. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: 1. Absolute neutrophil count \<1.5 × 109 /L. 2. Platelet count \<100 × 109 /L. 3. Hemoglobin \<9 g/dL (\<5.59 mmol/L). NOTE: any blood transfusion must be \>14 days prior to the determination of a haemoglobin ≥9 g/dL (≥5.59 mmol/L). 4. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) \>2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or \>5 × ULN in the presence of liver metastases. 5. Total bilirubin \>1.5 × ULN (participants with confirmed Gilbert's syndrome may be included in the study). 6. Creatinine \>1.5 × ULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \>1.5 × ULN. 15. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Participants with HIV that is controlled (not detectable viral load) with highly active antiretroviral therapy (HAART) are eligible to participate. Screening for chronic conditions is not required. 16. Prior treatment with AKT or PI3K inhibitors. 17. History of skin or gastrointestinal disorders that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of capivasertib. 18. History of hypersensitivity to active or inactive excipients of capivasertib, fulvestrant and LHRH agonists (if applicable, i.e., concomitant LHRH agonist required in this study) or drugs with a similar chemical structure or class to capivasertib, fulvestrant or LHRH agonists (if applicable, i.e., concomitant LHRH agonist required in this study). 19. History of intolerability to cetirizine or loperamide. 20. Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib. 21. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. 22. Evidence of dementia altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent.