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

NCT01723800 | Completed Phase 1 DMC

• 2 other identifiers: 12219NCI-2012-02161
• Study Type: interventional
• Target: 9
• 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 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

Conditions

Recurrent Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose, defined as the highest dose in which fewer than 33% of study participants experience a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) CTCAE version 4.0

  21 days

• Toxicity profile of PI3K inhibitor BKM120, assessed using NCI CTCAE version 4.0

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

  Up to 28 days after completion of study treatment

Secondary Outcomes (5)

• Pharmacokinetic (PK) parameters of PI3K inhibitor BKM120, carboplatin, and pemetrexed disodium in combination

  Days 1 and 8 of course 1

• Anti-tumor activity (complete response [CR] + partial response [PR]), assessed using RECIST

  Up to 28 days after completion of study treatment

• Disease control rate (CR + PR + stable disease [SD]), assessed using RECIST

  Up to 28 days after completion of study treatment

• Progression free survival

  6 months

• Overall survival

  1 year

Study Arms (1)

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

EXPERIMENTAL

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.

Drug: PI3K inhibitor BKM120; Drug: pemetrexed disodium; Drug: carboplatin; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: quality-of-life assessment

Interventions

PI3K inhibitor BKM120 DRUG

Given PO

Also known as: BKM120, PI3K_Inhibitor_BKM120, Buparlisib

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

pemetrexed disodium DRUG

Given IV

Also known as: ALIMTA, LY231514, MTA

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

quality-of-life assessment PROCEDURE

Ancillary studies

Also known as: quality of life assessment

Treatment (pemetrexed, carboplatin, PI3K inhibitor BKM120)

Eligibility Criteria

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

You may qualify if:

• Patients who have signed a written informed consent
• Patients must have a histologic or cytologic diagnosis of advanced, nonsquamous NSCLC (stage IV by American Joint Committee on Cancer \[AJCC\] 7th edition \[ed.\])
• Patients should not have received prior systemic chemotherapy for metastatic disease (prior epidermal growth factor receptor \[EGFR\], anaplastic lymphoma kinase \[ALK\], kinase inhibitor therapy is allowed); prior adjuvant or neoadjuvant therapy for early stage disease is allowed if received \>= 12 months prior to study entry
• Prior radiation therapy is allowed to \< 25% of the bone marrow; prior radiation must be completed at least 2 weeks prior to day 1 of cycle 1, and patients must have recovered from the acute toxic effects
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin (Hb) \> 9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium \>= the lower limit of normal (LLN)
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =\< 3 x upper limit of normal \[ULN\] if liver metastases are present)
• Serum bilirubin within normal range (or =\< 1.5 x ULN if liver metastases are present)
• Serum creatinine =\< 1.5 x ULN or calculated or 24-hour clearance \>= 45 mL/min (calculated creatinine clearance based on Cockcroft-Gault formula)

You may not qualify if:

• Patients who have received prior treatment with a P13K inhibitor or mammalian target of rapamycin (mTOR)-directed inhibitor
• Patients with a known hypersensitivity of BKM120 or to its excipients
• Patients with anaplastic lymphoma kinase (ALK) rearrangement or an activating epidermal growth factor receptor (EGFR) mutation who have not received and progressed on appropriate tyrosine kinase inhibitor therapy
• Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is \> 2 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry; stable corticosteroids treatment (e.g. dexamethasone 2 mg/day, prednisolone 10 mg/day) is permitted if it was initiated at least 14 days before start of study treatment
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patient has any of the following mood disorders as judged by the investigator or a psychiatrist, or as a result of the patient's mood assessment questionnaire:
• 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) or patients with active severe personality disorders (defined according to Diagnostic and Statistical Manual of Mental Disorders \[DSM\]-IV) are not eligible; NOTE: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug
• \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Meets the cut-off score of \>= 10 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of \>= 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Patients with diarrhea \>= CTCAE grade 2
• Left ventricular ejection fraction (LVEF) \< 50% as determined by echocardiogram (ECHO)
• Corrected QT interval (QTc) \> 480 msec on screening electrocardiogram (ECG) (using the Fridericia correction QTc \[QTcF\] 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

NVP-BKM120; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Karen Reckamp

  City of Hope Medical Center

  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 6, 2012
• First Posted: November 8, 2012
• Study Start: July 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 20, 2016

Record last verified: 2016-09

Locations

US (1)