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

Pancreatic Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03126435
• Other study ID #: CT4006
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2018
• Est. completion date: October 8, 2021

Study information

• Verified date: May 2023
• Source: SynCore Biotechnology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 218
• Est. completion date: October 8, 2021
• Est. primary completion date: July 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Pancreatic Cancer
• Metastatic Pancreas Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms

Intervention

Drug:
• EndoTAG-1
twice weekly
• Gemcitabine
once weekly

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
SynCore Biotechnology Co., Ltd.

Countries where clinical trial is conducted

United States,  France,  Hungary,  Israel,  Korea, Republic of,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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))
Other	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))
Primary	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	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)
Secondary	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)
Secondary	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.
Secondary	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)
Secondary	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)