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

NCT01540253 | Completed Phase 1 DMC

• 2 other identifiers: I 186510NCI-2011-00521
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) or recommended phase 2 dose of PI3K inhibitor BKM120

  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.

  21 days

• Incidence AE and tolerability of PI3-kinase inhibitor BKM120 in combination with docetaxel

  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.

  Up to 30 days after completion of treatment

Secondary Outcomes (3)

• Objective response rate (ORR) as assessed by the proportion of patients with a confirmed complete response (CR) or partial response (PR)

  Up to 6 courses

• Progression-free survival (PFS)

  Up to 3 years

• PK parameters of PI3-kinase inhibitor BKM120

  Baseline, days 1-7 of course 1, and then day 1 of all subsequent courses

Study Arms (1)

Treatment (enzyme inhibitor and chemotherapy)

EXPERIMENTAL

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.

Drug: PI3K inhibitor BKM120; Drug: docetaxel; Other: pharmacological study; Other: questionnaire administration; Other: laboratory biomarker analysis

Interventions

PI3K inhibitor BKM120 DRUG

Given PO

Also known as: BKM120, PI3K_Inhibitor_BKM120

Treatment (enzyme inhibitor and chemotherapy)

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Treatment (enzyme inhibitor and chemotherapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor and chemotherapy)

questionnaire administration OTHER

Ancillary studies

Treatment (enzyme inhibitor and chemotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor and chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
• Histologically or cytologically confirmed diagnosis of solid malignancy; patient should have locally advanced, inoperable or metastatic solid tumor with at least one site of measurable disease \[if applicable\] (per Response Evaluation Criteria in Solid Tumors \[RECIST\] for solid tumors or the appropriate disease classification/criteria for the target population)
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Life expectancy of \>= 12 weeks
• Platelet count \>= 100 x 10\^9/L
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 gm/dl
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within upper limits of normal (ULN) range (or =\< 3.0 x ULN if liver metastases are present)
• Serum bilirubin within ULN range (or =\< 1.5 x ULN if liver metastases are present; or total =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
• Serum creatinine =\< 1.5 x ULN or 24-hour clearance \>= 50 mL/min
• Serum amylase =\< ULN
• Serum lipase =\< ULN
• Fasting plasma glucose =\< 120 mg/dl
• International normalized ratio (INR) =\< 2
• Magnesium \>= the lower limit of normal

You may not qualify if:

• Previous anti-cancer chemotherapy, immunotherapy or investigational agents \< 4 weeks prior to the first day of study defined treatment; palliative radiation \< 2 weeks; patients who receive gamma knife radiosurgery for brain metastases are eligible if procedure was performed \> 4 weeks before treatment is started, is clinically stable and has been on stable low dose corticosteroid treatment (e.g. dexamethasone 2 mg/day, prednisolone 10 mg/day for at least 14 days before start of study treatment are eligible); ongoing hormonal therapies (luteinizing hormone-releasing hormone \[LHRH\] antagonists, megestrol) are allowed
• Previous treatment with a phosphatidylinositol 3-kinase (P1-3K) inhibitor
• Patients with a known hypersensitivity to BKM120 or to its excipients
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients have any of the following mood disorders as judged by the investigator or a psychiatrist, or who meets the cut-off score of \>= 12 in the Patient Health Questionnaire (PHQ-9) or a cut-off of \>= 15 in the Generalized Anxiety Disorder (GAD-7) mood scale, respectively, or selects a positive response of '1, 2, or 3' to questions number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
• \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Patients with diarrhea \>= CTCAE grade 2
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• Corrected QT interval (QTc) \> 480 msec on screening electrocardiogram (ECG) (using the QT interval corrected for Fridericia \[QTcF\] formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
• Conduction abnormality requiring a pacemaker

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Novartis: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Interventions

NVP-BKM120; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Alex Adjei

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: February 28, 2012
• Study Start: May 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (1)