BYL719 In Combination With Gemcitabine And (Nab)-Paclitaxel In Locally Advanced And Metastatic Pancreatic Cancer

Study Overview

BYL719 in Combination With Gemcitabine and (Nab)-Paclitaxel in Locally Advanced and Metastatic Pancreatic Cancer

The main purpose of this study is to see primarily if BYL719 is safe to be given to patients in combination with gemcitabine and nab-paclitaxel. Gemcitabine and nab-paclitaxel is an FDA-approved regimen to treat pancreatic cancer. Secondary goals will be to find out the effect on tumor of this new drug combination of BYL719, gemcitabine and nab-paclitaxel. In the first part of the study, different doses of BYL719 will be tested. In the second part of the study, all patients will be started at the same dose of BYL719.

N/A

Pancreatic Cancer

DRUG: BYL719
DRUG: Gemcitabine
DRUG: (nab)-paclitaxel

MCC-17815

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-06-02	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-04-06
First Submitted that Met QC Criteria 2014-06-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-04-08
First Posted (ACTUAL) 2014-06-04	Results First Posted N/A	Last Verified 2021-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel Dose escalation, followed by expansion, of BYL719 in combination with Gemcitabine and (Nab)-Paclitaxel. BYL719: once daily. Gemcitabine: Days 1,8, 15 of 28-day cycle. (Nab)-Paclitaxel: Days 1,8, 15 of 28-day cycle.	DRUG: BYL719 Dose escalation beginning at 250 mg/day DRUG: Gemcitabine Dose escalation beginning at 800 mg/m^2 DRUG: (nab)-paclitaxel 125 mg/m^2 dose

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Combination Therapy: BYL719, Gemcitabine, (Nab)-Paciltaxel

Dose escalation, followed by expansion, of BYL719 in combination with Gemcitabine and (Nab)-Paclitaxel. BYL719: once daily. Gemcitabine: Days 1,8, 15 of 28-day cycle. (Nab)-Paclitaxel: Days 1,8, 15 of 28-day cycle.

DRUG: BYL719

Dose escalation beginning at 250 mg/day

DRUG: Gemcitabine

Dose escalation beginning at 800 mg/m^2

DRUG: (nab)-paclitaxel

125 mg/m^2 dose

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	The MTD is defined as the highest dose level at which one or none of 6 patients experience a Dose Limiting Toxicity (DLT).	Up to 4 months per participant

Secondary Outcome Measures	Measure Description	Time Frame
Overall Response Rate (ORR)	Complete Response plus Partial Response (CR+PR). CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Up to 3 years
Overall Survival (OS)	Overall survival of patients who receive at least one dose of the study drug at MTD.	Up to 3 years
Progression-Free Survival (PFS)	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).	Up to 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patient is able to swallow and retain oral medication
Histologically documented diagnosis of pancreatic adenocarcinoma.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Required baseline laboratory status according to protocol document

Prior sensitivity or intolerance to PI3K inhibitors
Potential participants with central nervous system (CNS) involvement may participate if the patient is: >/= 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment; Clinically stable with respect to the CNS tumor at the time of screening; Not receiving steroid therapy.
Prior treatment with any cytotoxic chemotherapy for treatment of pancreatic cancer except as an adjuvant therapy. Should not have received gemcitabine within 6 months of starting the study treatment. 5-Fluorouracil or radiation treatment should be received more than 4 weeks prior to receiving the study drug.
Potential participants who have received radiotherapy ≤ 4 weeks prior to starting study drugs, with exception of palliative radiotherapy, who have not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated.
Potential participants who have undergone major surgery ≤ 4 weeks prior to starting study treatment or who have not recovered from side effects of such procedure.
Have received investigation agent within 30 days prior to enrollment
Clinically significant cardiac disease or impaired cardiac function
QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening ECG
Potential participants with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose (FPG)> 140 mg/dL or history of documented steroid-induced diabetes mellitus.
Any other condition that would, in the Investigator's judgment, preclude participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow oral medication, social/psychological complications.
Impaired GI function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-DNA and/or positive HbsAg, quantifiable hepatitis C virus [HCV]-RNA).
Known positive serology for human immunodeficiency virus (HIV)
Known severely impaired lung function (spirometry and diffusing capacity of lung for carbon monoxide[DLCO] 50% or less of normal and O2 saturation 88% or less at rest on room air).
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
Currently receiving treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A. Must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment. Switching to a different medication prior to starting study treatment is allowed.
Has a history of non-compliance to medical regimen or inability to grant consent
Currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment
History of another malignancy requiring active treatment within 2 years prior to starting study treatment, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
Participant who does not apply highly effective contraception during the study and through 12 weeks after final dose of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Novartis

Investigators

PRINCIPAL_INVESTIGATOR: Richard Kim, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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