Clinical trial NCT02468557: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Previously Untreated Pancreatic Ductal Adenocarcinoma
Relapsed/Refractory Pancreatic Ductal Adenocarcinoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-06-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
measure: Single-agent IDL: Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to last dose date (Maximum: 8 weeks) plus 30 days
measure: Idelalisib in Combination With Chemotherapy: Percentage of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Change From Baseline in FoxP3+ and Cluster Determinant 8+ (CD8+) Cells From Tumor Tissue Samples as a Measure of Pharmacodynamics Activity
timeFrame: Up to 2 years
measure: Idelalisib Plasma Concentrations Following Idelalisib 150 mg Twice Daily
timeFrame: 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
measure: Idelalisib Metabolite (GS-563117) Plasma Concentrations Following Idelalisib 150 mg Twice Daily
timeFrame: 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
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Clinical Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Goshen
country: United States
facility: Indiana University Goshen Center for Cancer Care
state: Indiana
city: Boston
country: United States
facility: Dana Farber/ Harvard Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Greenville
country: United States
facility: Greenville Hospital System
state: South Carolina
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.