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

Completed · Phase 1/Phase 2

Conditions studied: Metastatic Pancreatic Adenocarcinoma

In brief

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

Key facts

Study ID

NCT02985125

Run by

Georgetown University

People needed

12

Starts

2017-05-04

Expected to finish

2020-09-28

Last updated by the study team

2026-04-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed mPAC (mixed histology is acceptable as long as the predominant histology is pancreatic adenocarcinoma)
• Patient must consent to two mandatory biopsies and have tumor amenable to biopsy
• Measurable disease by RECIST v1.1 criteria (tumor ≥ 1 cm in longest diameter on axial image on CT or MRI and/or lymph node(s) ≥ 1.5 cm in short axis on CT or MRI) on baseline imaging
• Documented progression of disease on at least one 5-FU-based regimen and at least one GEM-based regimen for metastatic disease (progression during or within 3 months of the completion of adjuvant therapy is acceptable)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (see Table 2)
• Age ≥ 18 years
• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease
• Patients with available standard 12-lead ECG with the following parameters at screening (defined as the mean of the triplicate ECGs):
• QTcF interval at screening <450msec
• Resting heart rate 50-90bpm
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥100 × 109/L; hemoglobin ≥ 9.0 g/dL
• Patients may have a transfusion of red blood cells to meet the hemoglobin requirement
• Renal function: serum creatinine ≤ 1.5 × upper normal limit of institution's normal range or creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
• Hepatic function: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3.0 × the upper normal limit of institution's normal range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range. For subjects with liver metastases, AST and ALT < 5 × the upper normal limit of institution's normal range, and total bilirubin >1.5 - 3.0 x the upper normal limit of institution's normal range are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.
• Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper normal limit of institution's normal range and International Normalized Ratio (INR) < 1.5. Subjects on anticoagulant (such as warfarin) will be permitted to enroll as long s the INR is in the acceptable therapeutic range as determined by the investigator.
• Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
• Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Patient is capable of swallowing pills whole
• Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures

You may not qualify if…

• Patients previously exposed to, intolerant of, or ineligible for Cyclin-dependent kinase (CDK) inhibitors, Mammalian target of rapamycin (mTOR) inhibitors, and/or their combination
• Prior anti-tumor therapy within 3 weeks of Cycle 1 Day 1 (anti-tumor therapy defined as, but is not limited to, anti-cancer agents (cytotoxic chemotherapy, immunotherapy, and biologic therapy), radiotherapy, and investigational agents), the "wash-out period"
• 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.).
• Women who are pregnant or breastfeeding
• Concurrent use of CYP3A4 inhibiting or activating medications
• Concurrent use of an Angiotensin-converting enzyme (ACE) inhibitor (increased risk of angioedema with ACE inhibitors administered in combination with everolimus, seen in approximately 6.8% of patients)
• Psychiatric illness or social situation that would limit compliance with study requirements
• Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• 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.
• 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).
• Patient has a known history of HIV infection or chronic, active Hepatitis B (testing not mandatory).
• 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.).
• 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

Where it is running

• Lombardi Comprehensive Cancer Center — Washington D.C., District of Columbia, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.