Clinical trial NCT04825288: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer
Official title: A Phase I/II Randomized, Double-blind, Placebo-controlled Trial (1-BETTER) Examining XB2001 (Anti-IL-1⍺ True Human Antibody) in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Lead sponsor: XBiotech, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects in phase II portion will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).
Primary purpose: TREATMENT

Brief summary: This trial will include 2 portions (phase 1 and phase 2).

The first portion will be a Phase I, open label, dose escalation study to establish the maximum tolerated dose (MTD) of XB2001 as measured by Dose-Limiting Toxicity (DLT), in combination with ONIVYDE + LV + 5-FU chemotherapy regimen in patients with advanced pancreatic cancer and to determine the recommended dose for the subsequent Phase 2 study.

The phase 2 portion will be implemented with the maximum established tolerated dose (MTD) of XB2001. The target enrollment in the phase 2 portion is 60 patients which will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).

Detailed description: Study Title: A Phase I/II randomized, double-blind, placebo-controlled trial (1-BETTER) examining XB2001 (anti-IL-1⍺ True Human antibody) in combination with ONIVYDE + 5-FU/LV (+folinic acid) in advanced pancreatic cancer

Sponsor: XBiotech USA, Inc.

Study Chair: David Park, M.D.

Sample Size: Approximately 69 patients will be enrolled in the USA (at least 9 patients in the open label phase 1 portion and 60 patients in the randomized phase 2 portion)

Approximate Duration:

This trial will include 2 phases. The first portion will be a Phase I, open label, dose escalation study evaluating the safety, tolerability and establishing the Maximum Tolerated Dose (MTD) of XB2001 in at least nine patients with metastatic pancreatic adenocarcinoma who are receiving ONIVYDE + Leucovorin l + d racemic + 5-Fluorouracil chemotherapy treatment. The duration for each patient in the Phase I portion will be 14 days (1 treatment cycle) in which they will be given one intravenous dose of XB2001 prior to receiving ONIVYDE + Leucovorin l + d racemic + 5-Fluorouracil chemotherapy treatment and assessed for Dose Limited Toxicities (DLT). The Phase II portion will be implemented following the completion of the Phase I portion and declaration of the MTD. The duration of subject participation in the randomized, double-blind, placebo-controlled Phase II portion of the trial is approximately 28 weeks: including a screening period of up to 30 days, and 24-week treatment period. All study subjects can continue treatment with XB2001 in an open label extension, for as long as they are judged to be benefitting clinically and have had no unacceptable toxicities.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed pancreatic adenocarcinoma of exocrine pancreas that is metastatic, unresectable, or recurrent
* At least one measurable lesion according to Response Evaluation Criteria in Solid Tumor V1.1
* Documented disease progression after one prior gemcitabine-based therapy OR one FOLFIRINOX and gemcitabine combination therapy
* Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 or Karnofsky performance status (KPS) ≥ 70
* Adequate hepatic, renal and bone marrow function

Exclusion Criteria:

* Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration
* Clinically significant GI disorders
* Severe arterial thromboembolic events less than 6 months before inclusion
* Prior Whole Brain Radiation Therapy (WBRT)
* Evidence of brain metastases
* NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
* Use of strong CYP3A4 inducers or inhibitors and/or UGT1A1 inhibitors within 14 days prior to Visit 1/Baseline visit.

Primary outcomes:
measure: To establish the maximum tolerated dose (MTD) of XB2001 as measured by Dose-Limiting Toxicity (DLT), in combination with ONIVYDE + LV + 5-FU chemotherapy regimen in patients with advanced pancreatic cancer.
timeFrame: 44 days
measure: Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
timeFrame: 28 weeks
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first, assessed up to 24 weeks.
measure: Overall Survival (OS)
timeFrame: From baseline until the date of death (from any cause) assessed up to 24 weeks.
measure: Objective Response Rate
timeFrame: Assessment every 8 weeks after initial response assessed up to 24 weeks.
measure: Time to Treatment Failure
timeFrame: From baseline to treatment discontinuation (any cause) assessed up to 24 weeks
measure: Percentage of Patients with Clinical Benefit Response
timeFrame: Baseline to weeks 8, 16 and 24. CBR will be defined as a composite measure consisting of change in lean body mass (LBM) and change in quality of life
measure: Quality of Life assessed through the cancer-specific European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C30
timeFrame: Baseline to weeks 8, 16 and 24
measure: Number of Serious Adverse Events (SAEs)
timeFrame: From baseline (Visit 1) (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
measure: Incidence of Grade 3-4 Diarrhea
timeFrame: From Visit 1 (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
measure: Duration of hospitalizations
timeFrame: Baseline to weeks 4, 8, 12, 16, 20 and 24
measure: Plasma/serum concentration of XB2001
timeFrame: At the specified timepoints in the study calendar assessed up to 24 weeks
measure: Number of Treatment Cycles
timeFrame: Throughout the study assessed up to 24 weeks
measure: Change in (CD14+CD16+IL-1⍺+) triple positive tumor associated monocytes in peripheral blood
timeFrame: Baseline to week 2 (post infusion at visit 2)
Other outcomes:
measure: Results of a symptom questionnaire will be summarized by treatment arm at various post-infusion time points and compared over time
timeFrame: At various post-infusion time points assessed up to 22 weeks
measure: Cardiotoxicity measured by the number of required ECGs and cardiotoxicity related events summarized by treatment arm and compared over time
timeFrame: Compared over time, assessed up to 22 weeks
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Burbank
country: United States
facility: Disney Family Cancer Center at Providence St. Joseph Medical Center
state: California
city: Cerritos
country: United States
facility: TOI Clinical Research
state: California
city: Fullerton
country: United States
facility: Providence St. Joseph Heritage - Fullerton, CA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Grand Junction
country: United States
facility: Grand Valley Oncology
state: Colorado
city: Lake Mary
country: United States
facility: Sarah Cannon - Florida Cancer Specialists
state: Florida
city: Miami Beach
country: United States
facility: Mt. Sinai Comprehensive Cancer Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Merriam
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Revive Research - Farmington Hills
state: Michigan
city: Sterling Heights
country: United States
facility: Revive Research - Sterling Heights
state: Michigan
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Einstein Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Portland
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon - Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Midlothian
country: United States
facility: Bon Secours St. Francis Cancer Center
state: Virginia
Study officials:
affiliation: Providence St. Joseph Heritage
name: David J Park
role: STUDY_CHAIR
References: