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

Lilly

Status and phase: Completed; Phase 2

Conditions: Pancreatic Ductal Adenocarcinoma

Treatments: Drug: Gemcitabine; Drug: Abemaciclib; Drug: Capecitabine; Drug: LY3023414

Study type: Interventional

Funder types: Industry

Identifiers

NCT02981342

2016-002218-36 (EudraCT Number)

I3Y-MC-JPCJ (Other Identifier)

16342

Details and patient eligibility

About

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).

Enrollment: 106 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 3 patient groups

Abemaciclib

Experimental group

Description:

Abemaciclib given orally.

Treatment:

Drug: Abemaciclib

Abemaciclib + LY3023414

Experimental group

Description:

Abemaciclib given orally and LY3023414 given orally.

Treatment:

Drug: LY3023414

Drug: Abemaciclib

Standard of Care (Gemcitabine or Capecitabine)

Experimental group

Description:

Gemcitabine given intravenously (IV) OR capecitabine given orally.

Treatment:

Drug: Capecitabine

Drug: Gemcitabine