Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Recurrence

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Lymphoma, Non-Hodgkin

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

B-cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Indolent B Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Rituximab

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive BKM120 PO daily and rituximab IV. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with asymptomatic progression may continue treatment for up to 12 months. Pharmacodynamic samples from peripheral blood (for those with peripheral blood involvement) and bone marrow aspirate (for all patients) are drawn at baseline. Patients will undergo correlative studies to include bone marrow biopsy at study enrollment, and at the time of complete remission.

Will be supplied to each patient on the first day of each cycle. It will subsequently be self administered by the patient themselves daily on days 1-28 of every 28 day cycle

PI3K inhibitor BKM120

Given IV (intervenously) on days 2, 8, 15, and 22 of cycle 1, and subsequently on day 1 of cycles 3, 5, 7, 9, and 11.

rituximab

Pharmacodynamic samples from peripheral blood (for those with peripheral blood involvement) and bone marrow aspirate (for all patients) are drawn at baseline.

Pharmacodynamics

Patients will undergo correlative studies to include bone marrow biopsy at study enrollment, and at the time of complete remission. In addition, patients with peripheral blood involvement at enrollment will have peripheral blood drawn for all planned research correlates.

Correlative studies

Kami Maddocks, MD

This phase I clinical trial studies the side effects and the best dose of phosphatidylinositol-3-kinase (PI3K) inhibitor BKM120 when given together with rituximab in treating patients with relapsed or refractory low-grade B-cell lymphoma. PI3K inhibitor BKM120 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving PI3K inhibitor BKM120 with rituximab may be an effective treatment for B-cell lymphoma.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of combined rituximab and BKM120 (PI3k inhibitor BKM120) in patients with previously treated indolent non-Hodgkin lymphoma (NHL) (including follicular lymphoma (FL), marginal zone lymphoma, and lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia), and mantle cell lymphoma (MCL).

SECONDARY OBJECTIVES:

I. To determine specific toxicities associated with combined BKM120 and rituximab.

II. Evaluate for efficacy of BKM120 in combination with rituximab in these diseases.

OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120.

Patients receive PI3K inhibitor BKM120 orally (PO) daily on days 1-28 and rituximab intravenously (IV) on days 2, 8, 15, and 22 of course 1 and on day 1 of courses 3, 5, 7, 9, and 11. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with asymptomatic progression may continue treatment for up to 12 months.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

A Phase I Study of BKM120 and Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma

Explored using graphical analyses as well as summarized quantitatively.

Novartis

Principal Investigator

Docetaxel

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Patients receive PI3K inhibitor BKM120 PO QD and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

docetaxel

pharmacological study

questionnaire administration

laboratory biomarker analysis

Alex Adjei

This phase I trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with docetaxel in treating patients with advanced solid tumor that is locally advanced, cannot be removed by surgery, or metastatic. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PI3K inhibitor BKM120 together with docetaxel may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the dose-limiting toxicities and identify the recommended phase II dose of the combination of docetaxel and BKM 120 (P13K inhibitor BKM120) in patients with advanced solid tumors.

II. To determine the safety and tolerability of this combination. III. To determine any pharmacokinetic (PK) interaction between BKM12O and docetaxel.

SECONDARY OBJECTIVES:

I. To assess any preliminary evidence of efficacy with this combination in patients with advanced cancers.

II. To evaluate phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations as predictive biomarkers of efficacy for the combination.

III. To evaluate PIK3CA polymorphisms and polymorphisms in BKM120 transport and metabolism as predictors of toxicity and/or efficacy.

OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120.

Patients receive PI3K inhibitor BKM120 orally (PO) once daily (QD) and docetaxel intravenously (IV) over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

PI3K Inhibitor BKM120 and Docetaxel in Treating Patients With Advanced Solid Tumor That is Locally Advanced, Cannot Be Removed By Surgery, or Metastatic

A Phase I Study of the PI3-Kinase Inhibitor BKM120 in Combination With Docetaxel in Patients With Advanced Solid Tumors.

Adverse events (AE) will be coded and evaluated for severity using NCI CTCAE, version 4.0 and will be summarized by system organ class and preferred term.

AE will be coded and evaluated for severity using NCI CTCAE, version 4.0 and will be summarized by system organ class and preferred term.

The ORR will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients. Tumor response will be summarized for the evaluable patient population, and the 95% confidence interval for ORR (complete response \[CR\] + partial response \[PR\]) will be presented. Response will be evaluated by revised RECIST 1.1 criteria.

Roswell Park Cancer Institute

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on day 1, and PI3K inhibitor BKM120 PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may receive courses of PI3K inhibitor BKM120 alone or PI3K inhibitor BKM120 and pemetrexed disodium after 4-6 courses with carboplatin in the absence of unacceptable toxicity or disease progression.

pemetrexed disodium

carboplatin

quality-of-life assessment

Karen Reckamp

This phase I trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with carboplatin and pemetrexed disodium in treating patients with stage IV non-small cell lung cancer. PI3K inhibitor BKM120 and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PI3K inhibitor BKM120, carboplatin, and pemetrexed disodium together may kill more tumor cells

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of BKM120 (PI3K inhibitor BKM120) that can be administered in combination with carboplatin and pemetrexed (pemetrexed disodium) in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

II. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use of combination BKM120 and carboplatin and pemetrexed.

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetic parameters of BKM120, when used in combination with carboplatin and pemetrexed.

II. To obtain preliminary evidence of anti-tumor activity with this combination.

III. To evaluate downstream inhibition of the phosphatidylinositol 3 kinase (PI3K) pathway.

OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120. Patients receive pemetrexed disodium intravenously (IV) over 10 minutes followed by carboplatin IV over 30 minutes on day 1, and PI3K inhibitor BKM120 orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may receive courses of PI3K inhibitor BKM120 alone or PI3K inhibitor BKM120 and pemetrexed disodium after 4-6 courses with carboplatin in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed up for 28 days.

PI3K Inhibitor BKM120, Carboplatin, and Pemetrexed Disodium in Treating Patients With Stage IV Non-Small Cell Lung Cancer

Phase I Trial of BKM120 in Combination With Carboplatin and Pemetrexed in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Tables will be created to summarize all toxicities and side effects by dose, course, organ, and severity.

Means and 95% confidence intervals will be provided for the PK parameters.

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.

National Cancer Institute (NCI)

City of Hope Medical Center

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Musculoskeletal Diseases

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Nasopharyngeal Carcinoma

Laryngeal Diseases

Carcinoma, Verrucous

Laryngeal Neoplasms

Oropharyngeal Neoplasms

Squamous Cell Carcinoma of Head and Neck

Salivary Gland Neoplasms

Paranasal Sinus Neoplasms

Neoplasms, Unknown Primary

Tongue Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Otorhinolaryngologic Diseases

Otorhinolaryngologic Neoplasms

Pharyngeal Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Mouth Neoplasms

Mouth Diseases

Salivary Gland Diseases

Nasopharyngeal Neoplasms

Nasopharyngeal Diseases

Nose Neoplasms

Nose Diseases

Paranasal Sinus Diseases

Neoplasm Metastasis

Neoplastic Processes

Tongue Diseases

Laryngeal Cancer

Hypopharyngeal Cancer

Tongue Cancer

Metastatic Squamous Neck Cancer With Occult Primary

Oral Cancer

Cetuximab

Immunoglobulins, Intravenous

Patients receive PI3K inhibitor BKM120 PO QD 100 mg/day on days -7 to 0. Patients complete 1 week washout. 3 patients receive BKM120 PO 80mg / day and cetuximab 500 mg IV /14 days and after dose escalation, 9 patients receive BKM120 PO 100mg / day and cetuximab 500 mg IV /14 days thereafter.

All patients receive PI3K inhibitor BKM120 PO QD day on days 1-28 and cetuximab IV over 60-120 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

cetuximab

Tanguy Seiwert

This pilot randomized phase I/II trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with cetuximab and to see how well it works in treating patients with recurrent or metastatic head and neck cancer. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving PI3K inhibitor BKM120 together with cetuximab may kill more tumor cells

PRIMARY OBJECTIVES:

I. Induction of compensatory signaling/feedback loop signaling after one week of BKM120 (PI3K inhibitor BKM120) (run-in) compared to patients not treated with BKM120.

II. Safety and tolerability of combined treatment with BKM120 and cetuximab.

SECONDARY OBJECTIVES:

I. Induction of apoptosis after one week of BKM120 (run-in) compared to patients not treated with BKM.

II. Tumor shrinkage (based Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1 \[V1.1\] measurements) in patients treated with combination.

III. Response rate (based RECIST V1.1 measurements) in patients treated with combination.

IV. Overall survival. V. Progression free survival.

OUTLINE: This is a phase I, dose-escalation study of PI3K inhibitor BKM120, followed by a phase II study.

RUN-IN-PERIOD: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive PI3K inhibitor BKM120 orally (PO) once daily (QD) on days -7 to 0. Patients complete 1 week washout before dose escalation.

ARM II: Patients receive no treatment on days -7 to 0.

All patients receive PI3K inhibitor BKM120 PO QD on days 1-28 and cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

A Biomarker Driven Pilot Study of the Pan-class I PI3K Inhibitor NVP-BKM120 in Combination With Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer

Performed using snap frozen tissue samples using the well-established PamGene Kinase array platform available in the Salgia/Seiwert laboratories.

Maximum tolerated dose (MTD) is defined as the dose level preceding the dose in which greater than or equal to 2 out of 3-6 patients experience a dose limiting toxicity (DLT) assessed using CTCAE v4

Measured by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on Formalin-Fixed, Paraffin-Embedded (FFPE) sections in a descriptive manner.

Percentage of patients whose cancer shrinks or disappears after treatment.

Percentage of patients with prior EGFR failure assessed using RECIST whose cancer shrinks or disappears after treatment.

Tumor shrinkage will be visualized as a waterfall plot for graphical (qualitative) comparison.

Overall survival is defined as the time from study initiation to death due to any reason.

Progression free survival is defined as the time from study initiation to first evidence of progression of disease.

University of Chicago

Patients receive PI3K inhibitor BKM120 PO QD 100 mg/day on days -7 to 0. Patients complete 1 week washout. After dose escalation phase, 3 patients receive BKM120 PO 80mg / day and cetuximab 500 mg IV /14 days and 9 patients receive BKM120 PO 100mg / day and cetuximab 500 mg IV /14 days thereafter.

All patients receive PI3K inhibitor BKM120 PO QD day on days 1-28 and cetuximab IV over 60-120 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PI3K inhibitor BKM120: Given PO

cetuximab: Given IV

Arm I (BKM120 PO and Cetuximab 500 mg IV 14 Days)

Age, Continuous

Sex: Female, Male

White

African American

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr Everett Vokes, MD

Compensatory Signaling/Feedback Loop Signaling Evaluated by Measurement of Phosphorylated (p)-EGFR

0 patients out of 3 from the BKM 80mg/day cohort had DLT (dose limiting toxicities). 0 patients out of 9 from the BKM 100mg/day cohort had DLT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma	NCT02049541	Extranodal Marg... Nodal Marginal ... Recurrent Grade... Recurrent Grade... Recurrent Grade... Recurrent Mantl... Recurrent Margi... Splenic Margina... Waldenström Mac...	PI3K inhibitor ... rituximab Pharmacodynamic... Correlative stu...	18 Years -	Ohio State University Comprehensive Cancer Center
Study of BKM120 & Rituximab in Patients With Relapsed or Refractory Indolent B-Cell Lymphoma	NCT02049541	Extranodal Marg... Nodal Marginal ... Recurrent Grade... Recurrent Grade... Recurrent Grade... Recurrent Mantl... Recurrent Margi... Splenic Margina... Waldenström Mac...	PI3K inhibitor ... rituximab Pharmacodynamic... Correlative stu...	18 Years -	Ohio State University Comprehensive Cancer Center
PI3K Inhibitor BKM120 and Docetaxel in Treating Patients With Advanced Solid Tumor That is Locally Advanced, Cannot Be Removed By Surgery, or Metastatic	NCT01540253	Unspecified Adu...	PI3K inhibitor ... docetaxel pharmacological... questionnaire a... laboratory biom...	18 Years -	Roswell Park Cancer Institute
PI3K Inhibitor BKM120, Carboplatin, and Pemetrexed Disodium in Treating Patients With Stage IV Non-Small Cell Lung Cancer	NCT01723800	Recurrent Non-s... Stage IV Non-sm...	PI3K inhibitor ... pemetrexed diso... carboplatin laboratory biom... pharmacological... quality-of-life...	18 Years -	City of Hope Medical Center
PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer	NCT01816984	Metastatic Squa... Recurrent Metas... Recurrent Saliv... Recurrent Squam... Recurrent Squam... Recurrent Squam... Recurrent Squam... Recurrent Squam... Recurrent Squam... Recurrent Verru... Recurrent Verru... Salivary Gland ... Stage IV Squamo... Stage IV Squamo... Stage IVA Saliv... Stage IVA Squam... Stage IVA Squam... Stage IVA Squam... Stage IVA Squam... Stage IVA Verru... Stage IVA Verru... Stage IVB Saliv... Stage IVB Squam... Stage IVB Squam... Stage IVB Squam... Stage IVB Squam... Stage IVB Verru... Stage IVB Verru... Stage IVC Saliv... Stage IVC Squam... Stage IVC Squam... Stage IVC Squam... Stage IVC Squam... Stage IVC Verru... Stage IVC Verru... Tongue Cancer	PI3K inhibitor ... cetuximab	18 Years -	University of Chicago

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