Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Sirolimus

Temsirolimus

MTOR Inhibitors

Dactolisib

Tubulin Modulators

Antimitotic Agents

Increasing doses of oral BEZ235 100 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days.

Increasing doses of oral BEZ235 200 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days

Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.

BEZ235

The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given.

BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.

Novartis Pharmaceuticals

This is a prospective, multi-center, open-label, phase Ib/ II study (two parts) with patients that have locally advanced or metastatic HER2 negative breast cancer. The first part (phase Ib) will investigate the MTD / Recommended Phase 2 Dose (RP2D) of the combination therapy of BEZ235 twice daily (b.i.d.) and weekly paclitaxel using a Bayesian model. When MTD/ RP2D is established the second part (phase II) will start. Phase II will evaluate the efficacy and the safety of weekly paclitaxel alone compared to weekly paclitaxel plus BEZ235 bid.

Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer

A Dose-finding Phase Ib Study Followed by an Open-label, Randomized Phase II Study of BEZ235 Plus Paclitaxel in Patients With HER2 Negative, Inoperable Locally Advanced or Metastatic Breast Cancer

DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria.

The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the maximum tolerated dose (MTD).

Incidence of adverse events (based on CTCAE Version 4) summarized by system organ class and/or preferred term, severity and relation to study treatment.

PFS is defined as the time from start of treatment to objective tumor progression or death from any cause. Radiological assessments will be performed every 8 weeks.

Proportion of patients with a best overall response of CR or PR according to RECIST 1.1

Proportion of patients with a best overall response of CR, PR or SD with a duration of 24 weeks or longer according to RECIST 1.1

Hormones

Mitogens

This is a prospective, multi-center, open-label, single arm, phase II study with a 2-stage design and Bayesian interim monitoring to investigate the safety and efficacy of BEZ235 in patients with progressive metastatic HR+ HER2- breast cancer who have received at least one prior line of endocrine therapy and two to three prior lines of chemotherapy for metastatic disease. Patients will be stratified into 3 groups according to their PI3K (phosphatidylinositol 3-Kinase) pathway activation status.

BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer

A Phase II Study of Orally Administered BEZ235 Monotherapy in Patients With Hormone Receptor Positive, HER2 Negative, Metastatic Breast Cancer, With or Without PI3K Activated Pathway

Rare Diseases

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Phase I:

BKM 120 orally (PO) once daily (dose is 60mg or 80mg). Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks

Phase II:

BKM 120 orally (PO) once daily - dose is optimal dose determined in Phase I. Bevacizumab: 10mg/kg intravenous (IV) every 2 weeks

BKM120

Kent Shih, MD

In this phase I/II study,investigators are evaluating the feasibility and efficacy of the combination of BKM120, an oral inhibitor of PI3 kinase, and bevacizumab in the treatment of patients with relapsed/refractory GBM. In the Phase I part of the trial, the optimal BKM120 dose to be administered with a standard dose of bevacizumab will be determined in patients with refractory solid tumors. Although it is unlikely that the concurrent administration of bevacizumab will alter the pharmacokinetics of BKM120, limited pharmacokinetic sampling will be performed on all patients treated during the Phase II portion of the study. Assuming this combination is feasible, the Phase II portion of the study will proceed, using the doses determined in the Phase I portion. In the phase II portion, eligible patients will be limited to those with recurrent/progressive GBM following 1st line combined modality therapy.

This is an open-label, non-randomized Phase I study of patients with advanced refractory solid tumors followed by a Phase II study for the second-line treatment of patients with relapsed/refractory glioblastoma multiforme.

In the phase I part of the study the optimal dose of BKM120 when combined with bevacizumab was determined. In the Phase II part of this study, patients with relapsed/refractory GBM following first line therapy are being treated with the BKM120/bevacizumab combination. Limited BKM120 pharmacokinetic evaluation will be performed on all patients treated during this part of the study. Patients will be reevaluated for response to treatment after 2 cycles (8 weeks). Patients with objective response or stable disease will continue treatment, with subsequent reevaluations every 8 weeks, until disease progression or unacceptable toxicity occurs.

Two populations of patients with relapsed/refractory GBM will be treated in the Phase II trial: 1) patients with no previous exposure to bevacizumab (N= 55) and 2) patients who received bevacizumab as part of first-line combined modality treatment (N= 20).

Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme

Phase I/II Study of the Combination of BKM120 and Bevacizumab in Patients With Refractory Solid Tumors (Phase I) and Relapsed/Refractory Glioblastoma Multiforme (Phase II)

The optimal dose of BKM120 to administer in combination with standard dose bevacizumab determined as the dose at which ≤1 of 6 patients experiences a DLT assessed using NCI CTCAE v4.03 during Cycle 1 (28 days). The optimal dose of BKM120 was determined to be 60 mg by mouth (PO), once a day for each 28 day cycle along with bevacizumab, administered 10 mg/kg intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Two groups of patients in the Phase II trial will be considered separately, 1) participants who have not received previous bevacizumab and 2) participants who have received bevacizumab as part of first-line treatment. PFS is measured from the date of first protocol treatment until date of disease progression or death occurs, or date of last adequate tumor assessment using RANO or McDonald criteria. McDonald disease progression criteria: a 25% or greater increase in sum of the diameters of lesions, new lesions, or clinical deterioration (McDonald et al, 1990). RANO disease progression criteria: a 25% or greater increase in the enhancing lesions sum compared with smallest tumor measurement, significant increase in T2/FLAIR nonenhancing lesion on stable or increasing corticosteroids, new lesions, or clinical deterioration (Wen et al 2010)

Two groups of participants in the Phase II trial will be considered separately, 1) those who have not received previous bevacizumab and 2) those who have received bevacizumab as part of first-line treatment. Overall Response (OR) = number of patients with complete or partial responses (CR or PR) per McDonald or RANO criteria. McDonald: CR as disappearance of all disease for at least four weeks, no new lesions, no steroids; PR as 50% or greater decrease in the sum of all lesions compared with baseline for at least four weeks, no new lesions, stable or reduced steroids (McDonald 1990). RANO: CR as disappearance of all disease for at least 4 weeks, no new lesions, stable or improved nonenhancing lesions, and no steroid usage; and PR as a 50% or greater decrease in the sum of all lesions compared with baseline measurement for at least four weeks, no new lesions, stable or improved nonenhancing lesions on same or lower steroid dose compared to baseline (Wen 2010).

Two groups of patients in the Phase II trial will be considered separately, 1) participants who have not received previous bevacizumab and 2) participants who have received bevacizumab as part of first-line treatment. Overall survival is measured as the interval from first study treatment until date of death, or date last known alive.

Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.03

Novartis

SCRI Development Innovations, LLC

All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last dose of study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle

Phase I patients include those diagnosed with advanced, metastatic solid tumors.

Phase I - Dose Level 1 (60 mg BKM, 10mg/kg Bevacizumab)

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase I patients include those diagnosed with advanced, metastatic solid tumors.

Phase I - Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab)

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase II patients include those with progressive glioblastoma multiforme

Phase II - (60 mg BKM120, 10mg/kg Bevacizumab)

BKM120: 80mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase I patients include those diagnosed with advanced, metastatic solid tumors.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Primary Tumor Type

Phase I Outcomes do not utilize prior bevacizumab treatment status, thus number of participants with prior bevacizumab treatment not reported.

Prior Treatment with Bevacizumab

Patients that received at least one dose of study treatment

Charles Davis, RAC

Includes Phase I patients receiving 60 mg BKM120 and 10mg/kg bevacizumab.

Phase I Dose Level 1 (60 mg BKM120, 10mg/kg Bevacizumab)

Includes Phase I patients receiving 80mg BKM120 and 10mg/kg bevacizumab

Phase I Dose Level 2 (80 mg BKM120, 10mg/kg Bevacizumab)

Includes all Phase I patients receiving assigned study dosing.

Number of Phase I Patients Receiving 60mg or 80mg BKM120 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Optimal Dosage

Phase II patients previously treated with bevacizumab prior to enrolling in the study.

Study treatment:

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase II Patients With Prior Bevacizumab Treatment.

Phase II patients that had not previously been treated with bevacizumab prior to enrolling in the study.

Study treatment:

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase II Patients Without Prior Bevacizumab Treatment

All Phase II patients receiving at least one dose of study treatment that have had at least one post-baseline disease assessment

Median Progression-Free Survival (PFS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Phase II participants treated with bevacizumab as part of first-line treatment prior to enrolling in the study.

Study treatment:

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase II Participants - Prior Bevacizumab.

Phase II participants that have not received bevacizumab treatment prior to enrolling in the study.

Study treatment:

BKM120: 60mg by mouth (PO), once a day for each 28 day cycle. Bevacizumab: 10 mg/kg administered intravenously (IV) on Day 1 and Day 15 of each 28 day cycle.

Phase II Participants - Bevacizumab Naive

Includes participants in Phase II that receive at least one study treatment and have at least one post-baseline disease assessment.

Overall Response (CR or PR) of Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Phase II Participants - Prior Bevacizumab

Participants that have received at least one dose of study treatment

Median Overall Survival (OS) in Phase II Participants - Prior Bevacizumab and Bevacizumab Naive

Fatigue

Confusion

Hyperglycemia

Diarrhea

Alanine aminotransferase increased

Hypertension

Seizure

Asthenia

Aspartate Aminotransferase Increased

Hypertriglyceridemia

Abdominal pain

Altered Mental Status

Gait Disturbance

Ataxia

Lipase Increased

Muscle Weakness

Pneumonia

Sepsis

Respiratory Failure

Thrombocytopenia

Hypercholesterolemia

Mucositis

Anorexia

Memory Impairment

Pruritis

Vomiting

Mood Alteration

Weight Loss

Neutropenia

Dehydration

Dyspnea

Hemorrhage

Somnolence

Taste Alteration

Agitation

Dysarthria

Fall

Hypermagnesemia

Ejection Fraction Decreased

Elevated Liver Enzymes

Hypoalbuminemia

Hypophosphatemia

Psychosis

Suicidal Ideation

Thromboembolic Event

Akathisia

Cellulitis

Chronic Obstructive Pulmonary Disease

Delirium

Diabetic Ketoacidosis

Enteritis

Female Genital Tract Fistula

Gastrointestinal Infection

Hyperlipidemia

Intracranial Hemorrhage

Left Ventricular Systolic Dysfunction

Necrotizing Fasciitis

Palsy

Paralysis

Personality Change

Syncope

Transaminitis

Urine Output Decreased

Vaginal Fistula

Volume Depletion

Headache

Hypokalemia

Hyponatremia

Nausea

Proteinuria

Rash

Urinary Tract Infection

Includes all participants that received at least one dose of study treatment

Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety and Tolerability

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

This is a prospective multi-center, open-label, single arm, Phase II study to investigate the safety and efficacy of BKM120 in patients with advanced endometrial carcinoma whose disease progressed on or after a first-line antineoplastic treatment. Patients will receive BKM120 orally at a dose of 100 mg/day. Availability of tumor specimen (either archival tissue or a fixed fresh biopsy) is mandatory for assessment of the PI3K (Phosphatidylinositol 3 Kinase (PI3K) pathway activation status.

BKM120 as Second-line Therapy for Advanced Endometrial Cancer

A Phase II, Single-arm Study of Orally Administered BKM120 as Second-line Therapy in Patients With Advanced Endometrial Carcinoma

BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Overall survival (OS) was defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer	NCT01495247	Inoperable Loca... Metastatic Brea...	BEZ235 Paclitaxel	18 Years -	Novartis
BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer	NCT01288092	Metastatic Brea...	BEZ235	18 Years -	Novartis
Combination of BKM120 and Bevacizumab in Refractory Solid Tumors and Relapsed/Refractory Glioblastoma Multiforme	NCT01349660	Glioblastoma Mu...	Bevacizumab BKM120	18 Years -	SCRI Development Innovations, LLC
BEZ235 Trial in Patients With HER2-(Human Epidermal Growth Factor Receptor 2 Negative) /HR+ (Hormonal Receptor Positive) Metastatic Breast Cancer	NCT01288092	Metastatic Brea...	BEZ235	18 Years -	Novartis
BKM120 as Second-line Therapy for Advanced Endometrial Cancer	NCT01289041	Advanced Endome...	BKM120	18 Years -	Novartis
Phosphatidylinositol 3-kinase (PI3K) Alpha iNhibition In Advanced Breast Cancer	NCT02506556	Metastatic Brea...	BYl719	18 Years -	Peter MacCallum Cancer Centre, Australia

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