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

NCT02985125 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 2016-0232
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

Pancreas; 5-FU; Gemcitabine; LEE011; Everolimus; Refractory; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Progression-free survival

  2 years

• Overall survival (OS)

  2 years

• Best response in a patient using RECIST v1.1 criteria

  2 years

• Number of adverse events as accessed by NCI CTCAE v4.03

  2 years

Study Arms (5)

Phase I - Dose Level 1

EXPERIMENTAL

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; Drug: Everolimus

Phase I - Dose Level 2

EXPERIMENTAL

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; Drug: Everolimus

Phase I - Dose Level -1

EXPERIMENTAL

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; Drug: Everolimus

Phase I - Dose Level -2

EXPERIMENTAL

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; Drug: Everolimus

Phase II - Dose

EXPERIMENTAL

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; Drug: Everolimus

Interventions

LEE011 DRUG

Treatment cycles are 28 days long. It is taken orally. The dosage varies depending on the study arm.

Also known as: ribociclib

Phase I - Dose Level -1; Phase I - Dose Level -2; Phase I - Dose Level 1; Phase I - Dose Level 2; Phase II - Dose

Everolimus DRUG

Treatment cycles are 28 days long. It is taken orally. On all arms, the dosage will be 2.5mg.

Also known as: Afinitor®

Phase I - Dose Level -1; Phase I - Dose Level -2; Phase I - Dose Level 1; Phase I - Dose Level 2; Phase II - Dose

Eligibility Criteria

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

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.

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:

Sponsors & Collaborators

• Georgetown University: lead
• Novartis: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Cedars-Sinai Medical Center: collaborator
• Virginia Mason Hospital/Medical Center: collaborator

Study Sites (1)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

ribociclib; Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Benjamin Weinberg, MD

  Lombardi Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 7, 2016
• Study Start: May 4, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: May 21, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)