Phase 2
N=106
A Study of Abemaciclib (LY2835219) Alone or in Combination With Other Agents in Participants With Previously Treated Pancreatic Ductal Adenocarcinoma
Pancreatic Ductal Adenocarcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02981342 ↗Enrolled (actual)
106
Serious AEs
55.1%
Results posted
Jun 2019
Primary outcome: Primary: 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) — 15.2; 12.1; 36.4 percentage of Participants — p=0.0495
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Abemaciclib (Drug); LY3023414 (Drug); Gemcitabine (Drug); Capecitabine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eli Lilly and Company
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
15.2; 12.1; 36.4 | 0.0495 sig |
| PRIMARY Stage 2: Progression Free Survival (PFS) |
1.68; 1.81; 3.25 | 0.0085 sig |
| SECONDARY Stage 1: Objective Response Rate (ORR): Percentage of Participants With a Best Overall Response (BOR) of CR or PR |
3; 0; 3 | 1 |
| SECONDARY Stage 1: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and Its Metabolites (LSN2839567 (M2), LSN3106726 (M20)) |
356; 85.1; 153 | — |
| SECONDARY Stage 1: PK: Area Under the Curve (AUC) (AUC[Tau]) of LY3023414 |
— | — |
| SECONDARY Stage 1: PK: Maximum Concentration (Cmax) at Steady State of LY3023414 |
— | — |
| SECONDARY Stage 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD |
— | — |
| SECONDARY 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 |
3; 0; 3 | 1 |
| SECONDARY Stage 2: Duration of Response (DoR) |
— | — |
| SECONDARY Stage 2: Overall Survival (OS) |
2.71; 3.29; NA | 0.1938 |
| SECONDARY Stage 2: Change From Baseline in Carbohydrate Antigen 19.9 (CA 19-9) Level |
4281.53; 3225.29; -501.17 | — |
| SECONDARY Stage 2: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) |
0.63; -0.33; -0.02; 0.86; 0.18; 0.39 | 0.383 |
| SECONDARY 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) |
-6.21; -4.82; -2.40; -14.44; -11.65; -5.42 | 0.818 |
| SECONDARY Stage 1: PK: Steady State Trough Pre Dose Concentration of LY3023414 |
27.3 | — |
| SECONDARY Stage 1: PK: Mean Single Dose Concentration of LY3023414 at 2h Post-dose |
518 | — |
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).
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) 1.1.
- 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.
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).
Data sourced from ClinicalTrials.gov (NCT02981342). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.