An Adaptive, Open-Label, Randomized Phase 2 Study of Abemaciclib as a Monotherapy and in Combination With Other Agents Versus Choice of Standard of Care (Gemcitabine or Capecitabine) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Abemaciclib
- Conditions
- Pancreatic Ductal Adenocarcinoma
- Sponsor
- Eli Lilly and Company
- Enrollment
- 106
- Locations
- 13
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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.
Exclusion Criteria
- •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).
Arms & Interventions
Abemaciclib
Abemaciclib given orally.
Intervention: Abemaciclib
Abemaciclib + LY3023414
Abemaciclib given orally and LY3023414 given orally.
Intervention: Abemaciclib
Abemaciclib + LY3023414
Abemaciclib given orally and LY3023414 given orally.
Intervention: LY3023414
Standard of Care (Gemcitabine or Capecitabine)
Gemcitabine given intravenously (IV) OR capecitabine given orally.
Intervention: Gemcitabine
Standard of Care (Gemcitabine or Capecitabine)
Gemcitabine given intravenously (IV) OR capecitabine given orally.
Intervention: Capecitabine
Outcomes
Primary Outcomes
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)
Time Frame: Baseline to Measured Progressive Disease or Start of New Anticancer Therapy (Up to 6 Months)
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.
Stage 2: Progression Free Survival (PFS)
Time Frame: Baseline to Measured Progressive Disease or Death Due to Any Cause (Up to 6 Months)
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.
Secondary Outcomes
- 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 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414(Cycle 1 Day 1 through Cycle 4 Day 1 (28 Day Cycles))
- 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(Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 6 Months))
- Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR(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))(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 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)(Baseline to Death from Any Cause (Up to 10 Months))
- Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level(Baseline, 6 Months)
- Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)(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)(Baseline, 6 Months)
- Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414(C2D1: 0h, C3D1: 0h, C4D1: 0h)
- Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose(C1D1: 2h Post dose)