Buparlisib, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Advanced Solid Tumors

NCT01971489 | Withdrawn Phase 1

• 2 other identifiers: I 240413NCI-2013-01941
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best doses of buparlisib, gemcitabine hydrochloride, and cisplatin in treating patients with solid tumors that have spread to other places in the body. Buparlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving buparlisib, gemcitabine hydrochloride, and cisplatin may be a better treatment for solid tumors.

Conditions

Adult Solid Neoplasm; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs) using the National Cancer Institute (NCI) CTCAE version 4.0

  Adverse events 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 21 days

• Maximum-tolerated dose (MTD) defined as the maximum dose level at which less than or equal to 1 out of 6 patients have DLTs using NCI CTCAE version 4.0

  Up to 21 days

Secondary Outcomes (7)

• Disease control rate using RECIST (CR, PR, and SD)

  Up to 30 days after completion of study treatment

• Objective response rate (ORR) calculated as the number of patients with a confirmed complete response (CR) or partial response (PR) divided by the total number of patients using Response Evaluation Criteria in Solid Tumors (RECIST)

  Up to 30 days after completion of study treatment

• PIK3CA mutations

  Up to 30 days after completion of study treatment

• PIK3CA polymorphisms

  Up to 30 days after completion of study treatment

• PK effect of gemcitabine hydrochloride and cisplatin on buparlisib

  Pre-dose and at 0.5, 1, 2, and 4 hours post-dose on day 21 of course 1, and pre-dose and 0.5, 1, 2, and 4 hours post-dose on day 1 of course 2 (or day 3 of course 2 for the 2 days off, 5 days on dosing schedule)

Study Arms (1)

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

EXPERIMENTAL

Patients receive buparlisib PO QD on days 1-21, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Buparlisib; Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Questionnaire Administration

Interventions

Buparlisib DRUG

Given PO

Also known as: BKM120, PI3K Inhibitor BKM120

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Pharmacological Study OTHER

Correlative studies

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Questionnaire Administration OTHER

Ancillary studies

Treatment (buparlisib, gemcitabine hydrochloride, cisplatin)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of solid malignancy
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Life expectancy of \>= 12 weeks
• Platelet count \>= 150 x 10\^9/L
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 1.5 upper limit normal (ULN), or \< 3 x ULN if liver metastases are present
• Serum total bilirubin =\< ULN or 1.5 x ULN if liver metastases are present or total 3 x ULN with direct bilirubin =\< ULN in patients with well documented Gilbert syndrome
• Calculated or measured creatinine clearance \>= 60 mL/min
• Fasting plasma glucose \< 120 mg/dL
• Magnesium \>= the lower limit of normal
• Lipase =\< 1.5 ULN
• Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of study drug
• Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
• Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

You may not qualify if:

• Previous anti-cancer chemotherapy, immunotherapy or investigational agents \< 4 weeks, or palliative radiation \< 2 weeks prior to the first day of study treatment, or who have not recovered to grade 1 or better from related side effects of such therapy (except alopecia); patients who receive gamma knife radiosurgery for brain metastases are eligible if procedure was performed \> 2 weeks before treatment is started, is clinically stable and has been on stable low dose corticosteroid treatment (e.g., dexamethasone 2 mg/day, prednisolone 12 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 who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits
• Patient has a known hypersensitivity to any of the excipients of BKM120
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
• Patient is currently receiving increasing or chronic treatment (\> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (\> 5 days) can induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
• The following uses of corticosteroids are permitted: single doses; e.g. with standard premedication for taxanes; topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
• Patient is being treated at start of study treatment with any of the following drugs:
• Drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications
• Drugs with a known risk to induce Torsades de Pointes
• Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated; switching to a different medication prior to starting study treatment is allowed
• Patient is currently receiving warfarin or other Coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise; therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
• Patients who have other concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate patient participation in the clinical study (eg. active or uncontrolled severe infection, chronic active hepatitis, immunocompromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
• Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory) infection
• Patient has any of the following cardiac abnormalities:

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

NVP-BKM120; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine

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)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

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: October 23, 2013
• First Posted: October 29, 2013
• Study Start: September 1, 2015
• Primary Completion: August 1, 2016
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

US (1)