Clinical trial NCT03126435: EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Pancreas Cancer
Locally Advanced Pancreatic Cancer
Pancreatic Adenocarcinoma
Keywords: FOLFIRINOX
5-Fluorouracil
folinic acid
irinotecan
oxaliplatin
Gemcitabine
Lead sponsor: SynCore Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-04-24
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival
timeFrame: 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 outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization to either first observation of progressive disease or occurrence of death, up to approximately 33.5 months (assessed continuously during treatment)
measure: Percentage of Subjects With Objective Response
timeFrame: Up to approximately 33.5 months (assessed continuously during treatment)
measure: Duration of Response
timeFrame: 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.
measure: Percentage of Subjects With Disease Control According to RECIST v.1.1
timeFrame: Up to approximately 33.5 months (assessed continuously during treatment)
measure: Serum Carcinoma Antigen 19-9 (CA 19-9) Response Rate
timeFrame: Up to approximately 33.5 months (assessed at baseline, end of cycle 1 or the full treatment course)
Other outcomes:
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score
timeFrame: Up to approximately 33.5 months (assessed at baseline and end of treatment (EOT))
measure: Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score
timeFrame: Up to approximately 33.5 months (assessed at baseline and end of treatment (EOT))
Locations:
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group, Inc
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Columbus
country: United States
facility: John B. Amos Cancer Center / IACT Health
state: Georgia
city: Skokie
country: United States
facility: Orchard Healthcare Research (OHR) Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Investigator Clinical Research Centers of Indiana
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Tupelo
country: United States
facility: North Mississippi Hematology & Oncology Associates, Ltd.
state: Mississippi
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center (SNCC) - Central Clinic - Main Clinic
state: Nebraska
city: Sayre
country: United States
facility: Guthrie - Corning Hospital - Guthrie Cancer Center
state: Pennsylvania
city: North Charleston
country: United States
facility: Charleston Cancer Center
state: South Carolina
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Temple
country: United States
facility: Scott & White Vasicek Cancer Treatment Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatioclinical
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Hospital
state: Virginia
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHRU - Besançon
city: Bordeaux
country: France
facility: Hopital Haut Leveque
city: Brest
country: France
facility: CHRU Brest - Hôpital Morvan
city: Cholet
country: France
facility: Centre Hospitalier de Cholet
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Roche-sur-Yon
country: France
facility: Centre Hospitalier Départemental
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: La Timone
city: Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Paris
country: France
facility: Hopital La Pitié Salpétrière
city: Perpignan
country: France
facility: CH Saint Jean
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Strasbourg
country: France
facility: Clinique Sainte Anne/Strasbourg Oncologie Leberale
city: Budapest
country: Hungary
facility: Dél-pesti Centrumkórház - Országos Hematológia és Infektológia Intézet
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Megyei Kórház Onkoradiológiai Központ
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház
city: Pécs
country: Hungary
facility: Pécsi Tudomány Egyetem Onkoterápiás Intézet
city: Hadera
country: Israel
facility: Oncology Department, Hillel Yafe MC
city: Haifa
country: Israel
facility: Rambam Health Center
city: Kfar Sava
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Rabin MC
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Incheon-si
country: Korea, Republic of
facility: Inha University Hospital
city: Jeongnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Arkhangel'sk
country: Russian Federation
facility: Arkhangelsk Clinical Oncological Dispensary
city: Kursk
country: Russian Federation
facility: Kursk State Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution "Russian Oncological Scientific Center named after N.N.Blokhin"
city: Moscow
country: Russian Federation
facility: Private clinnic "Medicine 24/7"
city: Omsk
country: Russian Federation
facility: Budget Institution of Healthcare of Omsk Region "Clinical Oncology Dispensary"
city: Orenburg
country: Russian Federation
facility: State Budget Healthcare Institution "Orenburg Region Clinical Oncological Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: State Budgetary Healthcare Institution Leningrad Regional Oncology Center
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Branch
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital-Taipei Branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital (TSGH)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou Branch
Study officials:
affiliation: National Cheng Kung University Hospital,Tainan, Taiwan, R.O.C
name: Li-Tzong Chen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: