LEE011 Plus Everolimus In Patients With Metastatic Pancreatic Adenocarcinoma Refractory To Chemotherapy

Study Overview

LEE011 Plus Everolimus in Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy

This study is a single-arm, open-label, multi-institutional Phase I/II trial of the combination of LEE011 and everolimus in refractory mPAC.

This is a single arm, open label Phase I/II study to evaluate the progression free survival at 8 weeks (PFS8week) of the combination of LEE-011 plus everolimus, in patients with metastatic pancreatic cancer refractory to 5-fluorouracil (5-FU) and gemcitabine-based chemotherapy. Previous studies of third-line therapy in mPAC are limited but reveal stable disease in 25-31% of patients with no partial or complete responses (31% of patients in the GVAX/CRS-207 combination vaccine study had stable disease but only 52% of these patients were treated in the third-line setting). It is hoped that the combination of LEE-011 plus everolimus can increase the PFS8weeks to at least 50%, though early stopping rules are in place for lack of efficacy.

Metastatic Pancreatic Adenocarcinoma

DRUG: LEE011
DRUG: Everolimus

2016-0232

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 2016-11-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-05-20
First Submitted that Met QC Criteria 2016-12-02	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-05-21
First Posted (ACTUAL) 2016-12-07	Results First Posted N/A	Last Verified 2019-05

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:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase I - Dose Level 1 Treatment cycles are 28 days long. LEE011 (taken orally) - 250mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28	DRUG: LEE011 Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm. DRUG: Everolimus Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.
EXPERIMENTAL: Phase I - Dose Level 2 Treatment cycles are 28 days long. LEE011 (taken orally) - 300mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28	DRUG: LEE011 Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm. DRUG: Everolimus Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.
EXPERIMENTAL: Phase I - Dose Level -1 Treatment cycles are 28 days long. LEE011 (taken orally) - 200mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28	DRUG: LEE011 Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm. DRUG: Everolimus Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.
EXPERIMENTAL: Phase I - Dose Level -2 Treatment cycles are 28 days long. LEE011 (taken orally) - 150mg Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28	DRUG: LEE011 Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm. DRUG: Everolimus Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.
EXPERIMENTAL: Phase II - Dose Treatment cycles are 28 days long. LEE011 (taken orally) - the recommended phase II dose Once daily on days 1-21 Everolimus (taken orally) - 2.5mg Once daily on days 1-28	DRUG: LEE011 Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm. DRUG: Everolimus Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.

Primary Outcome Measures	Measure Description	Time Frame
Progression-free survival (PFS) rate at 8 weeks	PFS at 8 weeks in a patient with refractory mPAC treated with LEE011 and everolimus, defined as positive if a patient does not have evidence of progressive disease at 8 weeks as measured by expert radiologists using RECIST v1.1 criteria	8 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Progression-free survival	PFS in a patient with refractory mPAC treated with LEE011 and everolimus, defined as the time from Cycle 1, Day 1 to progressive disease (as measured by expert radiologists using RECIST v1.1 criteria), death from any cause, or last follow-up, as determined by the investigator of LEE011 and everolimus in patients with mPAC refractory to chemotherapy	2 years
Overall survival (OS)	Overall survival (OS) in a patient with refractory mPAC treated with LEE011 and everolimus, defined as the time from Cycle 1, Day 1 to death from any cause or last follow-up	2 years
Best response in a patient using RECIST v1.1 criteria	Best response in a patient, defined as the largest percent decrease in tumor size from baseline and categorized as a complete response, partial response, or stable disease by imaging studies, measured by expert radiologists using RECIST v1.1 criteria	2 years
Number of adverse events as accessed by NCI CTCAE v4.03	Adverse events in a patient with refractory mPAC treated with LEE011 and everolimus, defined as the number of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v4.03) that occur after Cycle 1, Day 1	2 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:

QTcF interval at screening <450msec
Resting heart rate 50-90bpm 9. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥100 × 109/L; hemoglobin ≥ 9.0 g/dL

At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases. 10. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 11. Patient has a known history of HIV infection or chronic, active Hepatitis B (testing not mandatory). 12. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.). 13. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:

History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
History of documented congestive heart failure (New York Heart Association functional classification III-IV)
Documented cardiomyopathy
Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular block (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block)
Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)
Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening 14. Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug (see Table 4 for details):

Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
Herbal preparations/medications, dietary supplements. 15. Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.

Collaborators and Investigators

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

Novartis
University of Texas Southwestern Medical Center
Cedars-Sinai Medical Center
Virginia Mason Hospital/Medical Center

Investigators

STUDY_CHAIR: Benjamin Weinberg, MD, Lombardi Comprehensive Cancer Center

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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