EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX

A Randomized Controlled, Open Label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1+GEM vs GEM Alone in Patients With Measurable Locally Advanced/Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment

The aim of this adaptive Phase 3 trial is to show a statistically significant superiority of EndoTAG-1 in combination with gemcitabine compared to gemcitabine monotherapy in patients with locally advanced/metastatic pancreatic cancer after FOLFIRINOX failure.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma; Metastatic Pancreas Cancer; Locally Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: EndoTAG-1; Drug: Gemcitabine

Detailed Description

The objective of the study was to assess the safety and efficacy of a combination therapy of EndoTAG-1 plus gemcitabine vs. gemcitabine monotherapy in patients with locally advanced and/or metastatic adenocarcinoma of the pancreas eligible for second-line therapy after failing first line therapy with FOLFIRINOX

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Besançon, France
    • CHRU - Besançon
  • Bordeaux, France
    • Hopital Haut Lévêque
  • Brest, France
    • CHRU Brest - Hopital Morvan
  • Cholet, France
    • Centre Hospitalier de Cholet
  • Dijon, France
    • Centre Georges François Leclerc
  • La Roche-sur-Yon, France
    • Centre Hospitalier Departemental
  • Lyon, France
    • Hopital Prive Jean Mermoz
  • Marseille, France
    • La Timone
  • Nancy, France
    • Institut de Cancerologie de Lorraine
  • Nice, France
    • Centre Antoine-Lacassagne
  • Paris, France
    • Hôpital La Pitié Salpêtrière
  • Perpignan, France, 66046
    • CH Saint Jean
  • Rennes, France
    • Centre Eugène Marquis
  • Strasbourg, France
    • Clinique Sainte Anne/Strasbourg Oncologie Leberale
• Hungary
  • Budapest, Hungary
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Budapest, Hungary
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary
    • Dél-pesti Centrumkórház - Országos Hematológia és Infektológia Intézet
  • Kecskemét, Hungary
    • Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
  • Miskolc, Hungary
    • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
  • Pécs, Hungary
    • Pécsi Tudomány Egyetem Onkoterápiás Intézet
• Israel
  • Hadera, Israel
    • Oncology Department, Hillel Yafe MC
  • Haifa, Israel
    • Rambam Health Center
  • Kfar Sava, Israel
    • Meir Medical Center
  • Petach Tikva, Israel
    • Rabin MC
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Korea, Republic of
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of
    • National Cancer Center
  • Incheon-si, Korea, Republic of
    • Inha University Hospital
  • Jeongnam, Korea, Republic of
    • Chonnam National University Hwasun Hospital
  • Seongnam, Korea, Republic of
    • CHA Bundang Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Suwon, Korea, Republic of
    • Ajou University Hospital
• Russian Federation
  • Arkhangel'sk, Russian Federation
    • Arkhangelsk Clinical Oncological Dispensary
  • Kursk, Russian Federation
    • Kursk State Clinical Oncology Dispensary
  • Moscow, Russian Federation
    • Federal State Budgetary Scientific Institution "Russian Oncological Scientific Center named after N.N.Blokhin"
  • Moscow, Russian Federation
    • Private clinnic "Medicine 24/7"
  • Omsk, Russian Federation
    • Budget Institution of Healthcare of Omsk Region "Clinical Oncology Dispensary"
  • Orenburg, Russian Federation
    • State Budget Healthcare Institution "Orenburg Region Clinical Oncological Dispensary"
  • Saint Petersburg, Russian Federation
    • State Budgetary Healthcare Institution Leningrad Regional Oncology Center
• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan
    • E-Da Hospital
  • Kaohsiung, Taiwan
    • Chang Gung Medical Foundation - Kaohsiung Branch
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital (TSGH)
  • Taipei, Taiwan
    • Mackay Memorial Hospital-Taipei branch
  • Taoyuan, Taiwan
    • Chang Gung Medical Foundation - Linkou Branch
• United States
  • California
    • Corona, California, United States, 92879
      • Compassionate Cancer Care Medical Group, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center / IACT Health
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research (OHR) Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46260-2082
      • Investigator Clinical Research Centers of Indiana
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Hematology & Oncology Associates, Ltd.
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Cancer Center (SNCC) - Central Clinic - Main Clinic
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840-1625
      • Guthrie - Corning Hospital - Guthrie Cancer Center
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Charleston Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Temple, Texas, United States, 76508
      • Scott & White Vasicek Cancer Treatment Center
    • The Woodlands, Texas, United States, 77380
      • Renovatioclinical
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University Of Virginia Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Written informed consent
3. Histologically or cytologically confirmed adenocarcinoma of the pancreas
4. Metastatic or locally advanced disease that is considered unresectable
5. Measurable / assessable disease according to RECIST v.1.1
6. Documented disease progression on first line FOLFIRINOX
7. Negative pregnancy test
8. Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential during the course of the study and for 90 days after last treatment (excluding women who are not of childbearing potential and men who have been sterilized).
9. ECOG performance status 0 or 1

Exclusion Criteria:

1. Cardiovascular disease, New York Heart Association (NYHA) III or IV
2. History of severe supraventricular or ventricular arrhythmia
3. History of coagulation or bleeding disorder
4. History of acute myocardial infarction within 6 months before randomization
5. History of congestive heart failure
6. Acute or chronic inflammation (autoimmune or infectious)
7. Significant active/unstable non-malignant disease likely to interfere with study assessments

8. Laboratory tests (hematology, chemistry) outside specified limits:

   1. WBC ≤ 3 x 10³/mm³
   2. ANC ≤ 1.5 x 10³/mm³
   3. Platelets ≤ 100.000/mm³
   4. Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)
   5. aPTT > 1.5 x ULN
   6. Serum creatinine > 2.0 mg/dl (> 176.8 μmol/l)
   7. AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN
   8. Alkaline phosphatase > 2.5 x ULN
   9. Total bilirubin > 2 x ULN
   10. Albumin < 2.5 g/dL
9. Clinically significant ascites
10. Any anti-tumor treatment (except FOLFIRINOX as the first-line therapy) for pancreatic adenocarcinoma before enrollment. Note: Patients who have undergone surgical interventions for pancreatic adenocarcinoma will be eligible.
11. Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field
12. Major surgery < 4 weeks prior to enrollment
13. Pregnant or nursing
14. Investigational medicinal product < 4 weeks of enrollment
15. Documented HIV history
16. Active hepatitis B infection requiring acute therapy Note: Subjects infected by the hepatitis B virus will be eligible for the study if they have no signs of hepatic decompensation and meet the liver function tests eligibility criteria.
17. Known hypersensitivity to any component of the EndoTAG-1 and/or gemcitabine formulations
18. History of malignancy other than pancreatic cancer < 3 years prior to enrollment, except nonmelanoma skin cancer or carcinoma in situ of the cervix treated locally
19. Vulnerable populations (e.g. subjects unable to understand and give voluntary informed consent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EndoTAG-1 and Gemcitabine; EndoTAG-1 22 mg/m² twice weekly plus Gemcitabine 1000mg/m² once weekly for 1 cycle (8 weeks) consisting of 3 weeks of treatment and 1 week rest followed by 3 weeks of treatment and 1 week rest until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent.	Drug: EndoTAG-1; twice weekly; Other Names: EndoTAG-1 was first developed by Munich Biotech AG (Germany) under the names LipoPac and MBT-0206 and by Medigene AG under the name of EndoTAG-1.; Drug: Gemcitabine; once weekly; Other Names: Gemcitabine Hydrochloride
Active Comparator: Gemcitabine Monotherapy; Gemcitabine 1000mg/m² once weekly, for 1 cycle (8 weeks) consisting of 3 weeks of treatment and 1 week rest followed by 3 weeks of treatment and 1 week rest until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent.	Drug: Gemcitabine; once weekly; Other Names: Gemcitabine Hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The efficacy of EndoTAG-1 treatment was demonstrated through number of events, meaning subject death, compared to number of subjects censored at the time of analysis.	From randomization to death from any cause or last day known to be alive, up to approximately 33.5 months (assessed continuously during treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The efficacy of EndoTAG-1 treatment was demonstrated through number of events, meaning first observation of progressive disease, compared to number of subjects censored at the time of analysis.	From randomization to either first observation of progressive disease or occurrence of death, up to approximately 33.5 months (assessed continuously during treatment)
Percentage of Subjects With Objective Response	Percentage of subjects with objective response is based on assessment of complete response (CR) or partial response (PR) according to RECIST v.1.1.	Up to approximately 33.5 months (assessed continuously during treatment)
Duration of Response	Duration of Response = (date of tumor progression or death - date of first objective response (CR or PR) +1) / 30.	From the first documentation of objective tumor response (date of the first CR or PR) to objective tumor progression or death due to any cause.
Percentage of Subjects With Disease Control According to RECIST v.1.1	Percentage of subjects with disease control is based on assessment of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST v.1.1	Up to approximately 33.5 months (assessed continuously during treatment)
Serum Carcinoma Antigen 19-9 (CA 19-9) Response Rate	Responders are defined as subjects with a reduction in CA 19-9 levels by least 50% from baseline to the end of cycle 1 (or end of full treatment course). If a subject died while on study, he/she was classified as a failure, regardless of previous assessments.	Up to approximately 33.5 months (assessed at baseline, end of cycle 1 or the full treatment course)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC). Questions include on altered bowled habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC. All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100; higher scores= greater degree of symptoms or treatment side effects and emotional issues.	Up to approximately 33.5 months (assessed at baseline and end of treatment (EOT))
Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score	Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30): included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/ vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score = better level of functioning or greater degree of symptoms. Change from baseline = Cycle/day score minus baseline score.	Up to approximately 33.5 months (assessed at baseline and end of treatment (EOT))

Collaborators and Investigators

• Sponsor: SynCore Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Li-Tzong Chen, M.D., Ph.D., National Cheng Kung University Hospital,Tainan, Taiwan, R.O.C

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2018
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): October 8, 2021

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Estimate): May 8, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Gemcitabine; oxaliplatin; irinotecan; 5-Fluorouracil; FOLFIRINOX; folinic acid
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: CT4006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No