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Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC (Trybeca-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03665441
Recruitment Status : Active, not recruiting
First Posted : September 11, 2018
Last Update Posted : February 15, 2021
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma

Tracking Information
First Submitted Date  ICMJE September 6, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date February 15, 2021
Actual Study Start Date  ICMJE September 15, 2018
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
Overall Survival (OS) [ Time Frame: 1 year after last patient randomized ]
To determine whether the addition of eryaspase to chemotherapy improves OS when compared to chemotherapy alone
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2018)
  • Progression Free Survival (PFS) [ Time Frame: 24 weeks after last patient randomized ]
    To compare PFS between the 2 treatment arm
  • Objective Response Rate (ORR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the ORR between the 2 treatment arms.
  • Duration of Response (DoR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the DoR between the 2 treatment arms
  • Disease Control Rate (DCR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the between the 2 treatment arms
  • Incidence of treatment emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Collected from time of informed consent until 30 days after last study treatment ]
    To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone by assessing the number of patients with with treatment emergent adverse events per CTCAE v5.0
  • Assess quality of life for global health status, functional scale and symptom scale using questionnaire EORTC QLQ-C30 [ Time Frame: 1 year after last patient randomized ]
    To assess patients quality of life using EORTC QLQ-C30 questionnaire by looking the change from baseline to end of study in the functional scale, symptom scale and global health status. Functional and symptom scale are scored from 1 to 4 and global health status is 7 point scale with higher score indicating worse status. For each scale, raw score will be calculated by averaging the individual values and a linear transformation applied to standardize the raw score.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • Progression Free Survival (PFS) [ Time Frame: 24 weeks after last patient randomized ]
    To compare PFS between the 2 treatment arm
  • Objective Response Rate (ORR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the ORR between the 2 treatment arms.
  • Duration of Response (DoR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the DoR between the 2 treatment arms
  • Disease Control Rate (DCR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the between the 2 treatment arms
  • Incidence of treatment emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Collected from time of informed consent until 30 days after last study treatment ]
    To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone by assessing the number of patients with with treatment emergent adverse events per CTCAE v5.0
  • Assess quality of life for global health status, functional scale and symptom scale using questionnaire EORTC QLQ-C30 [ Time Frame: 1 year after last patient randomized ]
    To assess patients quality of life using EORTC QLQ-C30 questionnaire by looking the change from baseline to end of study in the functional scale, symptom scale and global health status. Functional and symptom scale are scored from 1 to 4 and global health status is 7 point scale with higher score indicating worse status. For each scale, raw score will be calculated by averaging the individual values and a linear transformation applied to standardize the raw score.
  • Evaluate induction of anti-asparaginase antibodies and neutralizing antibodies [ Time Frame: 24 weeks after last patient randomized ]
    To assess the immunogenicity of eryaspase in terms of the induction of anti-asparaginase antibodies and neutralizing antibodies
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC
Official Title  ICMJE A Randomized, Phase 3 Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment of Patients With Pancreatic Adenocarcinoma
Brief Summary This is an open-label, multicenter, randomized, Phase 3 study in patients with ductal adenocarcinoma of the pancreas who have failed only one prior line of systemic anti-cancer therapy for advanced pancreatic cancer and have measurable disease.
Detailed Description

Patients who meet all inclusion and exclusion criteria will be randomized in a 1:1 ratio to one of the following treatment arms (see figure below):

  • Arm A (investigational arm): eryaspase in combination with either gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI [FOLinic acid-Fluorouracil-IRInotecan regimen] or Onivyde®/5 fluorouracil/leucovorin), or
  • Arm B (control arm): gemcitabine/Abraxane or irinotecan-based therapy (FOLFIRI or Onivyde/5-FU/leucovorin)

The chemotherapy will be investigator's choice and based on what patient has received in first line treatment. Treatment will continue until disease progression, unacceptable toxicity, or the patient's withdrawal of consent.

An End of Treatment visit should occur within approximately 30 days from last dose of eryaspase or chemotherapy regimen.

A survival follow-up period will include the collection of survival, progression of disease if applicable, treatment updates, and quality of life assessments every 8 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: eryaspase
    L-asparaginase encapsulated in erythrocytes (red blood cells)
    Other Name: L-asparaginase
  • Drug: Gemcitabine plus Abraxane
    gemcitabine, Abraxane
    Other Name: Gemzar, nab-paclitaxel, onxol
  • Drug: Irinotecan plus 5-FU plus leucovorin
    irinotecan, 5-FU, leucovorin
    Other Name: Onivyde, liposomal irinotecan, Camptosar, Campto, Adrucil, Carac, Efudex, Efudix, folinic acid, calcium folinate
Study Arms  ICMJE
  • Experimental: Eryaspase plus Chemotherapy

    eryaspase 100 U/kg dosed every 2 weeks in combination with

    Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle as follows:

    • Abraxane (125 mg/m2) IV
    • Gemcitabine (1000 mg/m2) IV

    Or

    Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle as follows:

    • Onivyde 70 mg/m2 (irinotecan freebase) IV (recommended dose in patients homozygous for UGT1A1*28 is 50 mg/m2)
    • Leucovorin 400 mg/m2 IV
    • 5 FU 2400 mg/m2

    Or

    • FOLFIRI: Irinotecan 180 mg/m2 IV
    • Leucovorin 400 mg/m² IV
    • 5 FU 400 mg/m² IV bolus
    • 5 FU 2400 mg/m² IV continuous infusion over 46 hours immediately following bolus 5 FU
    Interventions:
    • Drug: eryaspase
    • Drug: Gemcitabine plus Abraxane
    • Drug: Irinotecan plus 5-FU plus leucovorin
  • Chemotherapy alone
    Standard treatment: Gemcitabine plus abraxane (albumin-bound paclitaxel) administered on Days 1, 8, and 15 of each 4 week cycle Or Irinotecan plus 5-FU plus leucovorin administered on Days 1 and 15 of each 4 week cycle
    Interventions:
    • Drug: Gemcitabine plus Abraxane
    • Drug: Irinotecan plus 5-FU plus leucovorin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2018)
500
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
482
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

A patient will be eligible for the study if all the following criteria are met:

  1. Must be 18 years of age or older.
  2. Must have histologically confirmed pancreatic adenocarcinoma.
  3. Must have Stage III or IV disease.
  4. Must have received one line of systemic chemotherapy in the advanced setting with or without targeted agents, immunotherapy, or radiotherapy for treatment of advanced pancreatic adenocarcinoma.
  5. Must have radiological evidence of disease progression following most recent prior treatment, defined as appearance of any new lesion or increase of >20% of one or more existing lesions.
  6. Must have measurable lesion(s) per RECIST version 1.1 by CT scan with contrast (or MRI, if the patient is allergic to CT contrast media).

    NOTE: Bone disease consisting of blastic lesion only is not measurable.

  7. Archival or fresh tumor tissue must be available for evaluating relevant biomarkers. Formalin-fixed paraffin-embedded [FFPE] block preferred, or a minimum of 10 unstained FFPE slides of one archived block is required.

    NOTE: Cytology samples from fine needle aspirates or brushing biopsies are not sufficient.

    If archival tissue is unavailable and an elective biopsy can't be scheduled due to COVID, this will be waived.

  8. Must have adequate performance status:

    1. ECOG Performance Status (PS) score of 0, or
    2. ECOG PS score one and score ≥80 on Karnofsky Performance Status (KPS) scale. NOTE: Must have body mass index (BMI) ≥18.5 kg/m2 (obtained <14 days prior to randomization.
  9. Must have life expectancy of >12 weeks according to the investigator's clinical judgment.
  10. Females of childbearing potential must have a negative pregnancy test at screening and additional negative pregnancy test prior to first dose. Males and females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 6 months after the last dose of study treatment.
  11. Must have adequate laboratory parameters at baseline (obtained <14 days prior to randomization). Laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the medical monitor:

    1. Absolute neutrophil count ≥1.5 x 109/L.
    2. Hemoglobin ≥9 g/dL. Patients with a baseline Hemoglobin ≥13 g/dL should be discussed with the medical monitor.
    3. Platelet count ≥100,000/mm3 (100 x 109/L).
    4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (≤5 x ULN in presence of liver metastases).
    5. Total bilirubin ≤ 1.5 x institutional ULN.
    6. Serum creatinine within normal limits or calculated clearance >60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal range.
    7. Acceptable coagulation parameters: plasma antithrombin III >70% and fibrinogen ≥1.5 g/L
    8. Serum albumin ≥3.0 g/dL.
  12. Patients requiring biliary stent placement must have the biliary stent placed >7 days prior to screening and must have normalization of bilirubin level after stenting.
  13. Must not be receiving therapy in a concurrent clinical study and must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment. Patients taking part in surveys or observational studies are eligible to participate in this study.
  14. Must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent.

Exclusion Criteria:

A patient is not eligible to participate in the study if any of the following criteria are met:

  1. Resectable or borderline resectable pancreatic adenocarcinoma at the time of signing the informed consent.
  2. Histology other than pancreatic adenocarcinoma (for example, but not inclusive: neuroendocrine, adenosquamous, etc.).
  3. More than one line of prior treatment in advanced or metastatic setting.
  4. Patient has experienced medically significant acute decline in clinical status including

    1. Decline in ECOG PS to >1 (or KPS <70) between baseline visit and within 72 hours prior to randomization.
    2. Weight loss of ≥10% during screening.
  5. Presence of active or symptomatic untreated central nervous system (CNS) metastases.

    NOTE: Patients with asymptomatic or stable CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable, and the patient is off high-dose steroid treatment for at least one month prior to randomization.

  6. Prior radiotherapy to the only area of measurable disease. NOTE: Patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of eryaspase or chemotherapy.
  7. Bone as the only site of metastatic disease from pancreatic cancer (bone only disease).
  8. History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.

    NOTE: The revised Atlanta classification [1] requires that two or more of the following criteria be met for the diagnosis of acute pancreatitis: (a) abdominal pain suggestive of pancreatitis, (b) serum amylase or lipase level ≥3 x ULN, or (c) characteristic imaging findings using CT or MRI.

  9. Neurosensory neuropathy > Grade 2 at baseline.
  10. Pregnancy or breastfeeding.
  11. History of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.

    NOTE: Patients with unknown status of hepatitis B or C must be tested and declared negative before randomization.

  12. Hypersensitivity to any of the components of the chemotherapy or ASNase.
  13. Patients who have received live or live attenuated vaccines within 3 weeks of randomization.
  14. History of other malignancies NOTE: Adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix may be eligible.

    NOTE: Patients successfully treated for other malignancies and are disease-free for at least 5 years may be eligible.

  15. Any other severe acute or chronic condition/treatments that may increase the risk of study participation including:

    1. History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months prior to randomization.
    2. Current or history within 6 months prior to randomization of medically significant cardiovascular disease including symptomatic congestive heart failure >New York Heart Association (NYHA) Class II, unstable angina pectoris, clinically significant cardiac arrhythmia.
    3. Patients with pre-existing coagulopathy (e.g. hemophilia).
    4. Psychiatric illness/social situations or any other serious uncontrolled medical disorders in the opinion of the Investigator that would limit compliance with study requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03665441
Other Study ID Numbers  ICMJE GRASPANC 2018-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ERYtech Pharma
Study Sponsor  ICMJE ERYtech Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manuel Hidalgo, MD, PhD Weill Cornell, NY, US
Principal Investigator: Pascal Hammel, MD, PhD Hospital Beaujon, Clichy, France
PRS Account ERYtech Pharma
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP