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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03665441
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : January 29, 2020
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
Actual Study Start Date : September 15, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : April 2021

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 (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
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

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 (see APPENDIX 1).
  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).

    • Measurable disease may be in the field of prior irradiation; however, at least 4 weeks must have elapsed between the completion of radiation therapy and the baseline scan documenting disease status.
    • Bone disease is considered radiologically measurable only if there is at least a 50% lytic component.

    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.

  8. Must have adequate performance status (see APPENDIX 2 and APPENDIX 3):

    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. These include, but not limited to:

    a. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

    i. intravaginal

    ii. transdermal

    b. progestogen-only hormonal contraception associated with inhibition of ovulation:

    i. injectable

    ii. implantable

    c. intrauterine device (IUD)

    d. bilateral tubal occlusion

    e. vasectomised partner

    f. sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) is intended. The true abstinence is when this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]

    g. males with partners of childbearing potential must agree to use condoms

    NOTE: Since an indirect interaction between components of the oral contraceptives and ASNase cannot be ruled out, oral contraceptives are not considered acceptable as contraceptive methods in the current clinical trial. A method other than oral contraception should be used in women of childbearing potential.

    NOTE: All chemotherapeutic agents may be teratogenic and excreted in breast milk. Patients who are breast feeding should consider alternative methods.

  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%, fibrinogen ≥1.5 g/L, international normalized ratio (INR) <1.5, and partial thromboplastin time (PTT) ≤ institutional ULN.
    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.

    NOTE: Patients known to be homozygous for UGT1A1*28 who are assigned to an irinotecan-containing regimen must have the initial irinotecan dose reduced unless they have previously tolerated full doses of irinotecan. Subjects whose UGT1A1 status is not known but are being considered for irinotecan-based chemotherapy must be screened for UGT1A1*28 allele unless they have previously tolerated full doses of irinotecan before enrollment into the trial and must have the initial irinotecan dose reduced if demonstrated to be homozygous for the UGT1A1*28 allele.

    NOTE: Patients assigned to the irinotecan/5 FU arms in the study should not have dihydropyridine dehydrogenase deficiency (DPD). Patients whose DPD status is unknown at time of screening should be tested before enrollment in the irinotecan/5 FU arm unless they have previously tolerated full doses of 5 FU.

  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.

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: Nigel Biswas-Baldwin 857-706-1585 trybeca1-protocolinquiry@erytech.com

Locations
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United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
Principal Investigator: Niharika Mettu, MD         
France
Institut de Cancerologie Recruiting
Brest, France, 29609
Principal Investigator: Jean-Philippe Metges, MD         
Sponsors and Collaborators
ERYtech Pharma
Investigators
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Principal Investigator: Manuel Hidalgo, MD, PhD Weill Cornell, NY, US
Principal Investigator: Pascal Hammel, MD, PhD Hospital Beaujon, Clichy, France
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Responsible Party: ERYtech Pharma
ClinicalTrials.gov Identifier: NCT03665441    
Other Study ID Numbers: GRASPANC 2018-01
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
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:
Layout table for MeSH terms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Gemcitabine
Paclitaxel
Irinotecan
Albumin-Bound Paclitaxel
Asparaginase
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
Protective Agents
Vitamin B Complex