A Phase I/II Study of BGT226 in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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This is a phase I/II clinical research study with BGT226, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a Phase I dose escalation part followed by a safety expansion part and a Phase II expansion part. Once the MTD has been defined, the safety expansion and efficacy expansion parts of the trial will be opened for enrollment. Phase I safety expansion part will enroll advanced solid tumors. Phase II expansion part will enroll advanced breast cancer. An effort will be made to enrich the trial population with Cowden Syndrome patients with advanced solid malignancies.

Official Title
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A Phase I/II, Multi-center, Open-label Study of BGT226, Administered Orally in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer

Conditions
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Solid Tumors, Breast Cancer, Cowden Syndrome

Intervention / Treatment
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* Drug: BGT226


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All patients Histologically-confirmed, advanced solid tumors Progressive, recurrent unresectable disease Phase II expansion part (advanced breast cancer) Confirmed positive hormone receptor (estrogen receptor and/or progesterone receptor) or positive HER-2 expression status Disease progression/recurrence following hormonal or anti-HER-2 treatment for advanced disease At least one but not more than two prior chemotherapy regimens for the unresectable tumor Measurable disease by MRI or CT scan Cowden Syndrome patients with an advanced malignancy Genetic confirmation of Cowden Syndrome Age ≥ 18 World Health Organization (WHO) Performance Status of ≤ 2 Exclusion criteria: Hematopoietic: No diabetes mellitus or history of gestational diabetes mellitus No acute or chronic renal disease No acute or chronic liver disease No acute or chronic pancreatitis No impaired cardiac function or clinically significant cardiac diseases such as ventricular arrhythmia, congestive heart failure, uncontrolled hypertension No acute myocardial infarction or unstable angina pectoris within the past 3 months Not pregnant or nursing and fertile patients must use barrier contraceptives Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGT226<br> | Drug: BGT226<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of BGT226 (Phase I dose escalation) Safety and tolerability of BGT226 (all patients) Clinical tumor response in patients with advanced breast cancer (Phase II) |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics Changes in biological markers indicative of the inhibitory effect of BGT226. Changes in cellular physiology as assessed by Positron Emission Tomography (PET) imaging |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGT226, Advanced solid tumors (including sporadic and Cowden Syndrome) (Phase I part), Advanced breast cancer (including sporadic and Cowden Syndrome) (Phase II part), Solid tumors, Breast cancer, Cowden Syndrome, Phosphatidylinositol 3'-kinase (PI3K) inhibitor