EndoTAG-1 Plus Gemcitabine Versus Gemcitabine Alone in Patients With Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment

• Sponsor: SynCore Biotechnology Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03126435
• Collaborator: (none)
• Enrollment: 218
• Locations: 68
• Arms: 2
• Actual Duration (Months): 35.7
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreas Cancer; Locally Advanced Pancreatic Cancer; Pancreatic Adenocarcinoma	Drug: EndoTAG-1; Drug: Gemcitabine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled, Open Label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine Versus Gemcitabine Alone in Patients With Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment
• Actual Study Start Date: Oct 16, 2018
• Actual Primary Completion Date: Jul 30, 2021
• Actual Study Completion Date: Oct 8, 2021

Arms and Interventions

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; Drug: Gemcitabine; once weekly
Other: Gemcitabine 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

Outcome Measures

Primary Outcome Measures

1. Overall survival [1 year]

   Overall survival time is defined as time from randomization to death from any cause or last day known to be alive

Secondary Outcome Measures

1. Progression Free Survival [6 months]

   Progression Free Survival time is defined as the time from randomization to either first observation of progressive disease or occurrence of death

2. Percentage of subjects with Objective Response [1 year]

   Percentage of subjects with objective response is based on assessment of complete response (CR) or partial response (PR) according to RECIST v.1.1.

3. Duration of Response [1 year]

   Duration of Response is defined as the time 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.

4. Percentage of subjects with disease control according to RECIST v.1.1 [1 year]

   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

5. Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [1 year]

   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.

6. Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [1 year]

   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 bowel 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.

7. Serum Carcinoma Antigen 19-9 (CA 19-9) response rate [1 year]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

9. WBC ≤ 3 x 10³/mm³

10. ANC ≤ 1.5 x 10³/mm³

11. Platelets ≤ 100.000/mm³

12. Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)

13. aPTT > 1.5 x ULN

14. Serum creatinine > 2.0 mg/dl (> 176.8 μmol/l)

15. AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN

16. Alkaline phosphatase > 2.5 x ULN

17. Total bilirubin > 2 x ULN

18. Albumin < 2.5 g/dL

19. Clinically significant ascites

20. 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.

21. Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field

22. Major surgery < 4 weeks prior to enrollment

23. Pregnant or nursing

24. Investigational medicinal product < 4 weeks of enrollment

25. Documented HIV history

26. 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.

27. Known hypersensitivity to any component of the EndoTAG-1 and/or gemcitabine formulations

28. 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

29. Vulnerable populations (e.g. subjects unable to understand and give voluntary informed consent)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Compassionate Cancer Care Medical Group, Inc	Corona	California	United States	92879
2	Emory University Hospital	Atlanta	Georgia	United States	30322
3	John B. Amos Cancer Center / IACT Health	Columbus	Georgia	United States	31904
4	Orchard Healthcare Research (OHR) Inc.	Skokie	Illinois	United States	60077
5	Investigator Clinical Research Centers of Indiana	Indianapolis	Indiana	United States	46260-2082
6	Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)	Topeka	Kansas	United States	66606
7	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
8	Henry Ford Hospital	Detroit	Michigan	United States	48202
9	North Mississippi Hematology & Oncology Associates, Ltd.	Tupelo	Mississippi	United States	38801
10	Southeast Nebraska Cancer Center (SNCC) - Central Clinic - Main Clinic	Lincoln	Nebraska	United States	68510
11	Guthrie - Corning Hospital - Guthrie Cancer Center	Sayre	Pennsylvania	United States	18840-1625
12	Charleston Cancer Center	North Charleston	South Carolina	United States	29406
13	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104
14	Scott & White Vasicek Cancer Treatment Center	Temple	Texas	United States	76508
15	Renovatioclinical	The Woodlands	Texas	United States	77380
16	University of Virginia Hospital	Charlottesville	Virginia	United States	22908
17	CHU Angers	Angers		France
18	CHRU - Besançon	Besançon		France
19	Hopital Haut Leveque	Bordeaux		France
20	CHRU Brest - Hôpital Morvan	Brest		France
21	Centre Hospitalier de Cholet	Cholet		France
22	Centre Georges François Leclerc	Dijon		France
23	Centre Hospitalier Départemental	La Roche-sur-Yon		France
24	Hôpital Privé Jean Mermoz	Lyon		France
25	La Timone	Marseille		France
26	Institut de Cancérologie de Lorraine	Nancy		France
27	Centre Antoine-Lacassagne	Nice		France
28	Hopital La Pitié Salpétrière	Paris		France
29	CH Saint Jean	Perpignan		France	66046
30	Centre Eugène Marquis	Rennes		France
31	Clinique Sainte Anne/Strasbourg Oncologie Leberale	Strasbourg		France
32	Dél-pesti Centrumkórház - Országos Hematológia és Infektológia Intézet	Budapest		Hungary
33	Magyar Honvédség Egészségügyi Központ	Budapest		Hungary
34	Országos Onkológiai Intézet	Budapest		Hungary
35	Bács-Kiskun Megyei Kórház Onkoradiológiai Központ	Kecskemét		Hungary
36	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház	Miskolc		Hungary
37	Pécsi Tudomány Egyetem Onkoterápiás Intézet	Pécs		Hungary
38	Oncology Department, Hillel Yafe MC	Hadera		Israel
39	Rambam Health Center	Haifa		Israel
40	Meir Medical Center	Kfar Sava		Israel
41	Rabin MC	Petach Tikva		Israel
42	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel
43	Chungnam National University Hospital	Daejeon		Korea, Republic of
44	National Cancer Center	Goyang-si		Korea, Republic of
45	Inha University Hospital	Incheon-si		Korea, Republic of
46	Chonnam National University Hwasun Hospital	Jeongnam		Korea, Republic of
47	CHA Bundang Medical Center	Seongnam		Korea, Republic of
48	Korea University Guro Hospital	Seoul		Korea, Republic of
49	Samsung Medical Center	Seoul		Korea, Republic of
50	Severance Hospital	Seoul		Korea, Republic of
51	Ajou University Hospital	Suwon		Korea, Republic of
52	Arkhangelsk Clinical Oncological Dispensary	Arkhangel'sk		Russian Federation
53	Kursk State Clinical Oncology Dispensary	Kursk		Russian Federation
54	Federal State Budgetary Scientific Institution "Russian Oncological Scientific Center named after N.N.Blokhin"	Moscow		Russian Federation
55	Private clinnic "Medicine 24/7"	Moscow		Russian Federation
56	Budget Institution of Healthcare of Omsk Region "Clinical Oncology Dispensary"	Omsk		Russian Federation
57	State Budget Healthcare Institution "Orenburg Region Clinical Oncological Dispensary"	Orenburg		Russian Federation
58	State Budgetary Healthcare Institution Leningrad Regional Oncology Center	Saint Petersburg		Russian Federation
59	Changhua Christian Hospital	Changhua		Taiwan
60	Chang Gung Medical Foundation - Kaohsiung Branch	Kaohsiung		Taiwan
61	E-Da Hospital	Kaohsiung		Taiwan
62	China Medical University Hospital	Taichung		Taiwan
63	National Cheng Kung University Hospital	Tainan		Taiwan
64	Mackay Memorial Hospital-Taipei Branch	Taipei		Taiwan
65	National Taiwan University Hospital	Taipei		Taiwan
66	Taipei Veterans General Hospital	Taipei		Taiwan
67	Tri-Service General Hospital (TSGH)	Taipei		Taiwan
68	Chang Gung Medical Foundation - Linkou Branch	Taoyuan		Taiwan

Sponsors and Collaborators

• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: SynCore Biotechnology Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03126435
• Other Study ID Numbers: CT4006
• First Posted: Apr 24, 2017
• Last Update Posted: Apr 29, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by SynCore Biotechnology Co., Ltd.: FOLFIRINOX; 5-Fluorouracil; folinic acid; irinotecan; oxaliplatin; Gemcitabine
• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Gemcitabine

Study Results

No Results Posted as of Apr 29, 2022