What side effects are associated with this type of intervention?

Common side effects of breast cancer treatments similar to Afuresertib and Fulvestrant include hyperglycemia, diarrhea, rash, and fatigue from AKT inhibitors, and injection site pain, nausea, fatigue, and hot flashes from estrogen receptor antagonists. Combining these treatments may lead to overlapping toxicities like fatigue and gastrointestinal issues.

What prior FDA approvals exist?

The FDA has approved several treatments for hormone receptor-positive, HER2-negative breast cancer that combine targeted agents with endocrine therapy. Notably, the combination of CDK4/6 inhibitors (such as palbociclib, ribociclib, and abemaciclib) with endocrine therapies like letrozole or fulvestrant has been approved, showing significant improvements in progression-free survival. Additionally, the PI3K inhibitor alpelisib in combination with fulvestrant has been approved for patients with PIK3CA-mutated breast cancer. These approvals highlight the efficacy of combining targeted therapies with endocrine agents in treating advanced breast cancer.

What other types of research exist?

Promising alternatives to Afuresertib plus Fulvestrant for breast cancer patients include: 1) Palbociclib plus Fulvestrant, which has shown significant prolongation in PFS in the PALOMA-3 trial. 2) Everolimus plus Exemestane, which has demonstrated efficacy in hormone receptor-positive, HER2-negative disease. 3) Lenvatinib plus Pembrolizumab, which has shown improved PFS and OS in various cancers and may be considered for breast cancer treatment pending further studies.

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Protein Kinase Inhibitor

Afuresertib + Fulvestrant for Breast Cancer

Phase 1

Waitlist Available

Research Sponsored by Laekna LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with histologically or cytologically confirmed HR+/HER2- BC characterized by the absence of HER2 expression and the presence of ER and/or PR expression

Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion for an average of 12 months

Awards & highlights

Study Summary

This trial is testing a new combination therapy for patients with breast cancer who have failed 1-2 other treatments.

Who is the study for?

This trial is for adults with HR+/HER2- advanced or metastatic breast cancer who've had certain prior treatments. Participants must be post-menopausal or on ovarian suppression therapy, have a good performance status and life expectancy, and agree to use contraception. They can't join if they have heart issues, seizures, other serious health conditions, are pregnant/breastfeeding, or have used specific drugs recently.Check my eligibility

What is being tested?

The study tests the combination of afuresertib plus fulvestrant in patients whose breast cancer hasn't responded well to previous therapies. It's designed to see if this combo is effective and safe compared to standard treatments.See study design

What are the potential side effects?

While not specified here, common side effects may include reactions at the injection site from fulvestrant, gastrointestinal issues from oral medications like afuresertib, fatigue, possible liver function changes and potential hormonal imbalances.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is positive for hormone receptors and negative for HER2.

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I am fully active or can carry out light work.

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My blood, kidney, liver, clotting ability, and sugar levels are all within normal ranges.

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I can swallow pills and don't have stomach issues affecting medication absorption.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion for an average of 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion for an average of 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion for an average of 12 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Overall Response Rate (ORR) based on RECIST 1.1

Secondary outcome measures

Best Overall Response (BOR) based on RECIST 1.1

Disease Control Rate (DCR) based on RECIST 1.1

Duration of Response (DOR) based on RECIST 1.1

+4 more

Side effects data

From 2016 Phase 2 & 3 trial • 12 Patients • NCT02116803

50%

DECREASED APPETITE

30%

CONSTIPATION

30%

DIARRHOEA

30%

PAIN IN EXTREMITY

30%

RASH

20%

NASOPHARYNGITIS

20%

FATIGUE

20%

ANAEMIA

20%

ANGINA PECTORIS

20%

OEDEMA PERIPHERAL

20%

GAMMA-GLUTAMYLTRANSFERASE INCREASED

20%

HEADACHE

20%

COUGH

10%

BLOOD ALKALINE PHOSPHATASE INCREASED

10%

GASTROOESOPHAGEAL REFLUX DISEASE

10%

ASPARTATE AMINOTRANSFERASE INCREASED

10%

BLOOD CREATININE INCREASED

10%

INFLUENZA

10%

NAUSEA

10%

PLATELET COUNT DECREASED

10%

CONTUSION

10%

HYPERTRIGLYCERIDAEMIA

10%

LYMPHOCYTE COUNT DECREASED

10%

DYSPEPSIA

10%

DRY MOUTH

10%

PNEUMONIA

10%

HERPES ZOSTER

10%

ARTHRALGIA

10%

HYPOCALCAEMIA

10%

HYPERKALAEMIA

10%

EYE OEDEMA

10%

BRADYCARDIA

10%

CORONARY ARTERY DISEASE

10%

MYOCARDIAL ISCHAEMIA

10%

PLEURAL EFFUSION

10%

PNEUMOTHORAX

10%

INCREASED TENDENCY TO BRUISE

10%

LEUKOPENIA

10%

NEUTROPENIA

10%

HYPOTHYROIDISM

10%

ABDOMINAL PAIN

10%

ASTHENIA

10%

FACE OEDEMA

10%

PYREXIA

10%

INTERNATIONAL NORMALISED RATIO INCREASED

10%

ARTHRITIS

10%

MUSCLE SPASMS

10%

MUSCULOSKELETAL PAIN

10%

NEURALGIA

10%

INSOMNIA

10%

RESTLESSNESS

10%

DYSPNOEA

10%

DYSPNOEA EXERTIONAL

10%

PRODUCTIVE COUGH

10%

PRURITUS

10%

SKIN LESION

100%

80%

60%

40%

20%

Study treatment Arm

Dovitinib

Dovitinib+Fulvestrant

Trial Design

2Treatment groups

Experimental Treatment

Group I: Afuresertib and Fulvestrant Safety Run InExperimental Treatment1 Intervention

Safety run-in Cycle 1 (a cycle is 28 days) will be performed in the first 6 patients of the phase Ib. Combination regimens during the safety run-in period are: afuresertib 125 mg QD (once daily) or 125 mg Day1-21 Q4W + fulvestrant 500 mg or 250 mg Intra Muscular (IM) on Day 1, 15 of Cycle 1, and on Day 1 of the subsequent 28-day cycles.

Group II: Afuresertib and FulvestrantExperimental Treatment1 Intervention

Combination regimens are: afuresertib 125 mg QD (once daily) or 125 mg Day1-21 Q4W + fulvestrant 500 mg or 250 mg Intra Muscular (IM) on Day 1, 15 of Cycle 1, and on Day 1 of the subsequent 28-day cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Afuresertib

2014

Completed Phase 1

~30

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific pathways involved in cancer cell growth and survival. AKT inhibitors, like Afuresertib, block the AKT signaling pathway, which is crucial for cell proliferation and survival, thereby inducing cancer cell death. Estrogen receptor antagonists, such as Fulvestrant, bind to estrogen receptors on cancer cells, blocking estrogen from stimulating cancer growth. This is particularly important for hormone receptor-positive breast cancers. Other common treatments include aromatase inhibitors, which reduce estrogen production, and HER2 inhibitors, which target the HER2 protein overexpressed in some breast cancers. Understanding these mechanisms helps tailor treatments to the specific characteristics of a patient's cancer, potentially improving outcomes and minimizing side effects.

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial.An Experimental Analysis of the Molecular Effects of Trastuzumab (Herceptin) and Fulvestrant (Falsodex), as Single Agents or in Combination, on Human HR+/HER2+ Breast Cancer Cell Lines and Mouse Tumor Xenografts.A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer.