This is the first study where BAY1125976 is given to humans. Patients (all comers) will receive the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1125976. The relative bioavailability of liquid service formulation and tablets will be determined. After the MTD is defined breast cancer patients with and without AKT1 mutation will be treated. The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1125976. BAY1125976 will be given daily as single oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

NCT01915576

Conditions

1. Neoplasms

Interventions

1. Drug: BAY1125976
2. Drug: BAY1125976
3. Drug: BAY1125976

In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable - For expansion cohort only: Subjects with histologically or cytologically proven metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one line of chemotherapy in the metastatic setting and not amenable to surgery with curative intent - Subjects must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1) - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2 - Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study treatment - Subjects must provide tumor biopsies before treatment - Recovery to CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade 0 or Grade 1 or recovery to baseline preceding the prior treatment of any previous drug / procedure-related toxicity (except alopecia, anemia, and hypothyroidism) Exclusion Criteria: - History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II - Subjects with type 1 or type 2 diabetes mellitus - Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated hemoglobin (HbA1c) ≥ 7% - Moderate and severe hepatic impairment, i.e. --- E17K ---

In addition, the investigator must judge the experimental treatment as clinically and ethically acceptable - For expansion cohort only: Subjects with histologically or cytologically proven metastatic breast cancer (with and without AKT1 E17K (G49A) mutation) or subjects with known AKT1 E17K (G49A) mutation in any other advanced solid tumor with at least one line of chemotherapy in the metastatic setting and not amenable to surgery with curative intent - Subjects must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1) - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2 - Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study treatment - Subjects must provide tumor biopsies before treatment - Recovery to CTCAE (Common Terminology Criteria for Adverse Events Version 4.03) Grade 0 or Grade 1 or recovery to baseline preceding the prior treatment of any previous drug / procedure-related toxicity (except alopecia, anemia, and hypothyroidism) Exclusion Criteria: - History of cardiac disease including congestive heart failure > New York Heart Association (NYHA) Class II - Subjects with type 1 or type 2 diabetes mellitus - Subjects with fasting glucose >125 mg/dL in 2 independent measurements or glycated hemoglobin (HbA1c) ≥ 7% - Moderate and severe hepatic impairment, i.e. --- E17K --- --- G49A --- --- E17K ---

This study will test the recommended dose of AZD5363 (recommended from a previous phase 1 study of the drug) in patients with specific AKT mutations. In patients who have ER positive breast cancer with an AKT mutation, they will also be receiving a standard breast cancer drug called fulvestrant that is given as an injection. In patients who have prostate cancer with an AKT mutation, they will also be receiving a standard prostate cancer drug called enzalutamide that is taken orally.

NCT03310541

Conditions

1. Breast Cancer
2. Prostate Cancer
3. Advanced Solid Tumors

Interventions

1. Drug: AZD5363
2. Drug: Enzalutamide
3. Drug: Fulvestrant

MeSH:Prostatic Neoplasms Neoplasms

HPO:Neoplasm Prostate cancer Prostate neoplasm

condoms) Exclusion Criteria: - ER+ breast cancer patients harboring the AKT1 E17K mutation (patient population tested in MSK IRB# 14-214, study D3610C00001 part E, ClinicalTrials.gov --- E17K ---

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: The learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20 30 visits at the NIH. ...

NCT04316546

Conditions

1. Proteus Syndrome

Interventions

1. Drug: Miransertib (ARQ092)

MeSH:Proteus Infections Proteus Syndrome Syndrome

- Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib - Any experimental systemic therapy for the purpose of treating Proteus syndrome (e.g., sirolimus, everolimus, high dose steroids, alpelisib) within two weeks of the first dose of miransertib, except for participants who were previously or are currently treated with miransertib under a Compassionate Use/Expanded Access program or existing protocol --Participants who were previously treated with or currently are receiving miransertib will be enrolled and treated according to the Schedule of Assessments/Study Visits defined in this protocol - Intolerance of, or severe toxicity attributed to, AKT inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib) - Concurrent severe uncontrolled illness not related to Proteus syndrome - Ongoing or active infection - Known human immunodeficiency virus (HIV) infection malabsorption syndrome - Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements - Pregnant or breastfeeding (contraception requirements can be found above and in the informed consent form) - Inability to comply with study evaluations or to follow drug administration guidelines - Concomitant use of a prohibited medication - Regular tobacco use and/or use of cannabidiol/tetrahydrocannabidiol (CBD/THC), and/or vaping products Proteus Syndrome Proteus Infections Proteus Syndrome Syndrome Proteus syndrome is a rare mosaic overgrowth disorder caused by a somatic gain of function variant, c. 49G>A, p.(Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase. --- Glu17Lys ---