A Study Of Abemaciclib (LY2835219) Alone Or In Combination With Other Agents In Participants With Previously Treated Pancreatic Ductal Adenocarcinoma

Study Overview

A Study of Abemaciclib (LY2835219) Alone or in Combination With Other Agents in Participants With Previously Treated Pancreatic Ductal Adenocarcinoma

The purpose of this study is to evaluate the safety and efficacy of abemaciclib alone and in combination with other drugs versus standard of care in participants with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).

N/A

Pancreatic Ductal Adenocarcinoma

DRUG: Abemaciclib
DRUG: LY3023414
DRUG: Gemcitabine
DRUG: Capecitabine

16342
I3Y-MC-JPCJ (OTHER Identifier) (OTHER: Eli Lilly and Company)
2016-002218-36 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

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 2016-12-01	Results First Submitted 2019-04-18	Last Update Submitted that met QC Criteria 2019-11-06
First Submitted that Met QC Criteria 2016-12-01	Results First Submitted that Met QC Criteria 2019-05-31	Last Update Posted (ACTUAL) 2019-11-20
First Posted (ACTUAL) 2016-12-05	Results First Posted 2019-06-25	Last Verified 2019-08-18

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:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Abemaciclib Abemaciclib given orally.	DRUG: Abemaciclib Administered orally DRUG: LY3023414 Administered orally
EXPERIMENTAL: Abemaciclib + LY3023414 Abemaciclib given orally and LY3023414 given orally.	DRUG: Abemaciclib Administered orally DRUG: LY3023414 Administered orally
EXPERIMENTAL: Standard of Care (Gemcitabine or Capecitabine) Gemcitabine given intravenously (IV) OR capecitabine given orally.	DRUG: Gemcitabine Administered IV DRUG: Capecitabine Administered orally

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Abemaciclib

Abemaciclib given orally.

DRUG: Abemaciclib

Administered orally

DRUG: LY3023414

Administered orally

EXPERIMENTAL: Abemaciclib + LY3023414

Abemaciclib given orally and LY3023414 given orally.

DRUG: Abemaciclib

Administered orally

DRUG: LY3023414

Administered orally

EXPERIMENTAL: Standard of Care (Gemcitabine or Capecitabine)

Gemcitabine given intravenously (IV) OR capecitabine given orally.

DRUG: Gemcitabine

Administered IV

DRUG: Capecitabine

Administered orally

Primary Outcome Measures	Measure Description	Time Frame
Stage 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD)	Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)
Stage 2: Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization until first observation of objective progressive disease as defined by RECIST v1.1 or death from any cause, whichever comes first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a patient does not have a complete baseline disease assessment, then the PFS time will be censored at the randomization date, regardless of whether or not objectively determined disease progression or death has been observed for the patient; otherwise, if a patient is not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time will be censored at the last complete objective progression-free disease assessment date.	Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)

Secondary Outcome Measures	Measure Description	Time Frame
Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR	Objective response rate (ORR) is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.	Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up to 6 Months)
Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20))	Mean steady state exposure was reported as measured by maximum observed plasma concentration (Cmax).	Cycle(C)1 Day(D)14: 0 hour(h),0.5h,1h,2h,4h,6h,8h post dose
Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414		Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)
Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414		Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles)
Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD		Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)
Stage 2: Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months	Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD ≥6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.	Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months)
Stage 2: Duration of Response (DoR)		Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 6 Months)
Stage 2: Overall Survival (OS)	OS duration is measured from the date of randomization to the date of death from any cause. for participants who is not known to have died as of the data-inclusion cutoff date, OS was censored at the last known alive date. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.	Baseline to Death from Any Cause (Up to 10 Months)
Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level	No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.	Baseline, 6 Months
Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)	mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, and enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours, and typical completion time for this instrument is less than 5 minutes. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.	Baseline, 6 Months
Stage 2: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)	The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: 1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) 3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. No participants were enrolled to stage 2; however, results for stage 2 outcomes are reported from the data collected for participants enrolled to stage 1.	Baseline, 6 Months
Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414	Mean steady state exposure was reported by trough pre-dose plasma concentrations.	C2D1: 0h, C3D1: 0h, C4D1: 0h
Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose	Mean single dose exposure was reported by plasma concentrations collected approximately 2 hours post-dose.	C1D1: 2h Post dose

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:

Histological or cytological diagnosis of ductal adenocarcinoma of the pancreas.
Metastatic disease with documented disease progression following previous treatment with at least one, but no more than 2 prior therapies, with one of the prior therapies having been either gemcitabine-based or fluoropyrimidine-based therapy. Neoadjuvant and/or adjuvant therapies for localized resectable or unresectable PDAC each count as a line of therapy if multiagent chemotherapy regimens were administered (and neoadjuvant regimen was different than adjuvant regimen) and if the participant progressed with metastatic disease while taking or within 6 months of completion of (neo)adjuvant therapy.
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Participant for whom treatment with monotherapy chemotherapy such as gemcitabine or capecitabine is a reasonable choice.
Discontinued all prior treatment for cancer at least 14 days prior to initial dose of study treatment.
Adequate organ function.

allow alanine aminotransferase (ALT) or aspartate aminotransferase (AST) up to 5x upper limit of normal (ULN) if liver metastases.
allow bilirubin up to 2.5 times ULN if elevation is not associated with other signs of liver toxicity or can be explained by mechanical obstruction - requires clinical research physician approval.

Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: Participants with controlled atrial fibrillation for >30 days prior to study treatment initiation are eligible.
Have insulin-dependent diabetes mellitus. Participants with type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c (HbA1c) <7%.
Have symptomatic central nervous system metastasis. Screening of asymptomatic participants is not required for enrollment.
Have had major surgery within 7 days prior to initiation of study drug to allow for postoperative healing of the surgical wound and site(s).
Have previously received treatment with any cyclin-dependent kinase (CDK) 4 and 6 inhibitor or phosphatidylinositol 3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor or have a known hypersensitivity to any component of the investigational products in this study.
Have a known hypersensitivity to investigator's choice of standard of care (gemcitabine or capecitabine).

Collaborators and Investigators

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

Investigators

STUDY_DIRECTOR: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications

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