Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma

A Phase 1b Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma

The primary objective of this study is to evaluate the safety of single agent idelalisib and to evaluate safety and define the maximum tolerated dose (MTD) of idelalisib in combination with chemotherapy in adults with metastatic pancreatic ductal adenocarcinoma.

Study Overview

• Status: Terminated
• Conditions: Previously Untreated Pancreatic Ductal Adenocarcinoma; Relapsed/Refractory Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Idelalisib; Drug: Nab-paclitaxel; Drug: mFOLFOX6

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Clinical Research Institute
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Indiana
    • Goshen, Indiana, United States, 46506
      • Indiana University Goshen Center for Cancer Care
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber/ Harvard Cancer Institute
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:

  • Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR
  • Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin
• Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1
• Prior systemic chemotherapy treatment for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib single agent only)
• Received one prior line of chemotherapy for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + mFOLFOX6 only)

• Adequate organ function defined as follows:

  • Hepatic: Total bilirubin ≤ 1.25 x upper limit of normal (ULN) (Arm: idelalisib + nab-paclitaxel ); total bilirubin ≤1.5 x ULN (Arm: single agent idelalisib and Arm: idelalisib + mFOLFOX6); aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT), alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) < 2.5 x ULN, and albumin > 3.0 g/dL
  • Hematological: absolute neutrophil count (ANC) > 1,500 cells/cubic millimetre (m^3), platelet > 100,000 cells/mm^3, hemoglobin > 9.0 grams/decilitre (g/dL)
  • Renal: Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) > 30 millilitre (ml)/min as calculated by the Cockcroft-Gault method
• Able to comprehend and willing to sign the written informed consent form

Key Exclusion Criteria:

• Currently or previously treated with biologic, or immunotherapy
• Currently or previously treated with conventional chemotherapy, or other agents for metastatic pancreatic ductal adenocarcinoma (Arm: idelalisib + nab-paclitaxel only)
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
• Known human immunodeficiency viruses (HIV) infection
• History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to enrollment, adequately treated Stage 1 or 2 non-pancreatic cancer currently in complete remission, or any other non-pancreatic cancer that has been in complete remission for ≥ 5 years
• Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or cystadenocarcinoma
• History of serious allergic reaction, including anaphylaxis and toxic epidermal necrolysis
• Presence of peripheral neuropathy ≥ Grade 2 (Arm: idelalisib + nab-paclitaxel and Arm: idelalisib + mFOLFOX6)
• Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, congestive heart failure [New York Heart Association > Class III]) within 6 months or enrollment
• Known hypersensitivity to idelalisib, its metabolites, or formulation excipients
• Known hypersensitivity to nab-paclitaxel (Arm: idelalisib + nab-paclitaxel), their metabolites, or formulation excipients
• Known hypersensitivity to 5-fluorouracil, leucovorin, or oxaliplatin (Arm: idelalisib + mFOLFOX6), their metabolites, or formulation excipients

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Idelalisib 150 mg; Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101
Experimental: Idelalisib + nab-paclitaxel; Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + nab-paclitaxel.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; Drug: Nab-paclitaxel; 125 mg/m^2 administered intravenously on Days 1, 8 and 15 of each 28 day cycle
Experimental: Idelalisib + mFOLFOX6; Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + mFOLFOX6.	Drug: Idelalisib; Tablets administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL-101; Drug: mFOLFOX6; mFOLFOX6 will be administered intravenously on Days 1 and 15 of each 28 day cycle. This regimen consists of levoleucovorin 200 milligram/meter per square (mg/m^2) or racemic leucovorin 400 mg/m^2, oxaliplatin 85 mg/m^2, bolus 5-fluorouracil 400 mg/m^2, and a 46 hour infusion of 5-fluorouracil 2, 400 mg/m^2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	TEAEs were defined as adverse events (AEs) with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the study drug. It also included the AEs that led to premature discontinuation of study drug.	First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post baseline time point, up to and including the date of last dose of study drug plus 30 days. If the relevant baseline laboratory value was missing, any abnormality of at least Grade 1 observed within the time frame specified above was considered treatment emergent. Severity grade is defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening). The percentage of participants for any post-baseline abnormal laboratory value in the Grade 1-4 category is reported. The term 'hypo' indicates less than the normal count of a parameter and 'hyper' indicates more than the normal count of a parameter.	First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
Idelalisib in Combination With Chemotherapy: Percentage of Participants With Dose Limiting Toxicities (DLTs)	Dose limiting toxicities were defined as toxicities experienced during the first 28 days of treatment (Cycle 1) that were judged to be clinically significant and at least possibly related to study treatment.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity		Up to 2 years
Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily		Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 hours (h) postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose
Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily		Cycle 1, Day 1: Predose and 0.5, 1, 1.5, 2, 3, 4, and 8 h postdose; Day 8: Predose and 1.5 h postdose; Day 15: Predose and 1.5 h postdose Cycle 2, Day 1: Predose and 1.5 h postdose
Overall Response Rate (ORR)	Overall response rate (ORR) was defined as the percentage of participants who achieved a Complete Response (CR) or Partial Response (PR) as assessed by response evaluation criteria in sold tumors (RECIST) v1.1.	Up to 2 years
Overall Survival (OS)	Overall survival is defined as the interval from first dose date of study drug to death from any cause.	Up to 2 years
Progression Free Survival (PFS)	Progression free survival is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.	Up to 2 years

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Borazanci E, Pishvaian MJ, Nemunaitis J, Weekes C, Huang J, Rajakumaraswamy N. A Phase Ib Study of Single-Agent Idelalisib Followed by Idelalisib in Combination with Chemotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma. Oncologist. 2020 Nov;25(11):e1604-e1613. doi: 10.1634/theoncologist.2020-0321. Epub 2020 Jun 18.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2015
• Primary Completion (Actual): April 27, 2016
• Study Completion (Actual): April 27, 2016

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: June 10, 2015
• First Posted (Estimate): June 11, 2015

Study Record Updates

• Last Update Posted (Actual): April 2, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Idelalisib
• Other Study ID Numbers: GS-US-385-1577

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No