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

Primary Purpose

Previously Untreated Pancreatic Ductal Adenocarcinoma, Relapsed/Refractory Pancreatic Ductal Adenocarcinoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Idelalisib
Nab-paclitaxel
mFOLFOX6
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Previously Untreated Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Scottsdale Healthcare Clinical Research Institute
  • Cedars Sinai Medical Center
  • University of Colorado Cancer Center
  • Georgetown University
  • Indiana University Goshen Center for Cancer Care
  • Dana Farber/ Harvard Cancer Institute
  • University of Rochester
  • Greenville Hospital System
  • Mary Crowley Medical Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Idelalisib 150 mg

Idelalisib + nab-paclitaxel

Idelalisib + mFOLFOX6

Arm Description

Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.

Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + nab-paclitaxel.

Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + mFOLFOX6.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity
Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily
Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily
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.
Overall Survival (OS)
Overall survival is defined as the interval from first dose date of study drug to death from any cause.
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.

Full Information

First Posted
June 8, 2015
Last Updated
March 31, 2021
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02468557
Brief Title
Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma
Official Title
A Phase 1b Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Study Start Date
July 30, 2015 (Actual)
Primary Completion Date
April 27, 2016 (Actual)
Study Completion Date
April 27, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Previously Untreated Pancreatic Ductal Adenocarcinoma, Relapsed/Refractory Pancreatic Ductal Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Idelalisib 150 mg
Arm Type
Experimental
Arm Description
Participants were administered with idelalisib (IDL) 150 mg tablets orally, twice daily (morning and evening) for 8 weeks.
Arm Title
Idelalisib + nab-paclitaxel
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + nab-paclitaxel.
Arm Title
Idelalisib + mFOLFOX6
Arm Type
Experimental
Arm Description
Participants will receive escalating doses of idelalisib at a dose level of up to 150mg + mFOLFOX6.
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
GS-1101, CAL-101, Zydelig®
Intervention Description
Tablets administered orally twice daily
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Intervention Description
125 mg/m^2 administered intravenously on Days 1, 8 and 15 of each 28 day cycle
Intervention Type
Drug
Intervention Name(s)
mFOLFOX6
Intervention Description
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.
Primary Outcome Measure Information:
Title
Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
Title
Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Description
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.
Time Frame
First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
Title
Idelalisib in Combination With Chemotherapy: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Description
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.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity
Time Frame
Up to 2 years
Title
Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily
Time Frame
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
Title
Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily
Time Frame
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
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
Overall survival is defined as the interval from first dose date of study drug to death from any cause.
Time Frame
Up to 2 years
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Scottsdale Healthcare Clinical Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Indiana University Goshen Center for Cancer Care
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46506
Country
United States
Facility Name
Dana Farber/ Harvard Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Greenville Hospital System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32356383
Citation
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.
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Study of Single Agent Idelalisib Followed by Idelalisib in Combination With Chemotherapy in Adults With Metastatic Pancreatic Ductal Adenocarcinoma

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