Cisplatin, Etoposide and PI3K Inhibitor BKM120 in Treating Patients With Advanced Solid Tumors or Small Cell Lung Cancer

NCT02194049 | Completed Phase 1 DMC

• 4 other identifiers: UCDCC#239470970CBKM120ZUS38TNCI-2014-00218
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Extensive Stage Small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events of combining daily BKM120 with cisplatin and etoposide as graded by the National Cancer Institute (NC) CTCAE version 4.0

  The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, time of onset (i.e. course number), duration, and reversibility or outcome.

  Up to 28 days post-treatment

Secondary Outcomes (5)

• MTD defined as the highest dose tested in which fewer than 33% of patients experience DLT attributed to the study drugs when at least 6 patients were treated at that dose, as graded by NCI CTCAE version 4.0

  21 days

• Response rate assessed by computed tomography (CT) scan based on Response Evaluation Criteria In Solid Tumors (RECIST)

  Up to 30 days

• Overall survival

  Up to 30 days

• Time to progression (TTP) based on RECIST

  Up to 30 days

• Pharmacokinetic analysis

  Baseline, at 1, 2, 4, 6, and 24 hours of day 1 of course 1, baseline day 15 of course 1, and at 1 and 2 hours post-dose on day 1 of course 2

Study Arms (1)

BKM 120, cisplatin, etoposide

EXPERIMENTAL

Patients receive PI3K Inhibitor BKM120 PO QD on days 1-21, cisplatin IV over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: BKM120; Drug: cisplatin; Drug: etoposide

Interventions

BKM120 DRUG

Given PO

Also known as: PI3K_Inhibitor_BKM120

BKM 120, cisplatin, etoposide

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

BKM 120, cisplatin, etoposide

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

BKM 120, cisplatin, etoposide

Eligibility Criteria

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

You may qualify if:

• Histological or cytological proven advanced solid tumors
• =\< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve)
• ECOG performance status =\< 2
• 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
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =\< 3.0 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; or total bilirubin =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Serum creatinine =\< 1.5 x ULN or calculated clearance \>= 60 mL/min
• Serum albumin \>= 3 g/dl
• Serum amylase =\< ULN
• Serum lipase =\< ULN

You may not qualify if:

• Received prior treatment with a P13K inhibitor
• Received \> 300 mg/m\^2 of cisplatin and/or for whom cisplatin would not be beneficial
• Prior treatment with any investigational drug within the preceding 3 weeks
• Known hypersensitivity to BKM120 or to its excipients
• Untreated brain metastases are excluded
• Acute or chronic liver, renal disease or pancreatitis
• Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire
• Diarrhea \>= CTCAE grade 2
• Active cardiac disease
• History of cardiac dysfunction
• Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus
• Other concurrent severe and/or uncontrolled concomitant medical conditions
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated
• Treated with any hematopoietic colony-stimulating growth factors
• Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug

Sponsors & Collaborators

• University of California, Davis: lead
• Novartis: collaborator

Study Sites (1)

University of California at Davis Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Interventions

NVP-BKM120; Cisplatin; Etoposide

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Karen Kelly

  University of California, Davis

  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: July 10, 2014
• First Posted: July 18, 2014
• Study Start: July 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: June 1, 2016
• Last Updated: January 9, 2018

Record last verified: 2016-06

Locations

US (1)