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

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ClinicalTrials.gov Identifier: NCT03665441
Recruitment Status : Not yet recruiting
First Posted : September 11, 2018
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma

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.

Condition or disease Intervention/treatment Phase
Pancreatic Adenocarcinoma Drug: eryaspase Drug: Gemcitabine plus Abraxane Drug: Irinotecan plus 5-FU plus leucovorin Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 3 Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment of Patients With Pancreatic Adenocarcinoma
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 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
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

Active Comparator: Chemotherapy alone
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
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 24 weeks after last patient randomized ]
    To compare PFS between the 2 treatment arm

  2. Objective Response Rate (ORR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the ORR between the 2 treatment arms.

  3. Duration of Response (DoR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the DoR between the 2 treatment arms

  4. Disease Control Rate (DCR) [ Time Frame: 24 weeks after last patient randomized ]
    To compare the between the 2 treatment arms

  5. 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

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must be 18 years of age or older.
  2. Must have histologically confirmed pancreatic ductal adenocarcinoma.
  3. Must have Stage III or IV disease.
  4. Must have received only one line of systemic chemotherapy 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.
  6. Must have measurable lesion(s).
  7. Archival or fresh tumor tissue must be available for evaluating relevant biomarkers.
  8. Must have adequate performance status: ECOG score of 0 or 1.
  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 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 hematologic, chemistry and coagulation laboratory parameters at baseline.
  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.
  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:

  1. Resectable or borderline resectable pancreatic adenocarcinoma.
  2. Patient has experienced medically significant acute decline in clinical status including

    1. Decline in ECOG PS to >1 (or KPS <70)
    2. Weight loss of ≥10% during screening.
  3. Presence of active or symptomatic untreated central nervous system (CNS) metastases.
  4. Prior radiotherapy to the only area of measurable disease.
  5. Bone as the only site of metastatic disease from pancreatic cancer.
  6. History of recent clinical pancreatitis.
  7. Neurosensory neuropathy >Grade 1 at baseline.
  8. Pregnancy or breastfeeding.
  9. History of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.
  10. Hypersensitivity to any of the components of the chemotherapy or asparaginase.
  11. Patients being treated with warfarin are not eligible. Warfarin must be replaced with low molecular weight heparin.
  12. History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by surgery alone or surgery plus radiotherapy with no evidence of disease for >5 years.
  13. Any other severe acute or chronic condition that may increase the risk of study participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03665441


Contacts
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Contact: Hedy Dion 857-706-1590 trybeca1-protocolinquiry@erytech.com

Sponsors and Collaborators
ERYtech Pharma
Investigators
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Principal Investigator: Manuel Hidalgo, MD, PhD Beth Israel Deconess Medical Center, MA, US
Principal Investigator: Pascal Hammel, MD, PhD Hospital Beaujon, Clichy, France

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Responsible Party: ERYtech Pharma
ClinicalTrials.gov Identifier: NCT03665441     History of Changes
Other Study ID Numbers: GRASPANC 2018-01
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ERYtech Pharma:
pancreatic
cancer
asparaginase
gemcitabine
Abraxane
asparagine depletion
onivyde
nab-paclitaxel
folinic acid
fluorouracil
irinotecan
leucovorin
amino acid
RECIST 1.1
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Folic Acid
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Irinotecan
Asparaginase
Levoleucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Antidotes