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

• ClinicalTrials.gov Identifier: NCT03126435
• Recruitment Status: Completed
• First Posted: April 24, 2017
• Results First Posted: March 24, 2023
• Last Update Posted: May 6, 2023
• Sponsor: SynCore Biotechnology Co., Ltd.
• Information provided by (Responsible Party): SynCore Biotechnology Co., Ltd.

Tracking Information

• First Submitted Date: April 19, 2017
• First Posted Date: April 24, 2017
• Results First Submitted Date: November 7, 2022
• Results First Posted Date: March 24, 2023
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: October 16, 2018
• Actual Primary Completion Date: July 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 4, 2022)

Overall Survival [ Time Frame: From randomization to death from any cause or last day known to be alive, up to approximately 33.5 months (assessed continuously during treatment) ]

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.

Original Primary Outcome Measures (submitted: April 19, 2017)

Overall survival [ Time Frame: 1 year ]

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

Current Secondary Outcome Measures (submitted: December 4, 2022)

• Progression Free Survival (PFS) [ Time Frame: From randomization to either first observation of progressive disease or occurrence of death, up to approximately 33.5 months (assessed continuously during treatment) ]
  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.
• Percentage of Subjects With Objective Response [ Time Frame: Up to approximately 33.5 months (assessed continuously during treatment) ]
  Percentage of subjects with objective response is based on assessment of complete response (CR) or partial response (PR) according to RECIST v.1.1.
• Duration of Response [ Time Frame: 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. ]
  Duration of Response = (date of tumor progression or death - date of first objective response (CR or PR) +1) / 30.
• Percentage of Subjects With Disease Control According to RECIST v.1.1 [ Time Frame: Up to approximately 33.5 months (assessed continuously during treatment) ]
  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
• Serum Carcinoma Antigen 19-9 (CA 19-9) Response Rate [ Time Frame: Up to approximately 33.5 months (assessed at baseline, end of cycle 1 or the full treatment course) ]
  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.

Original Secondary Outcome Measures (submitted: April 19, 2017)

• Progression Free Survival [ Time Frame: 6 months ]
  Progression Free Survival time is defined as the time from randomization to either first observation of progressive disease or occurrence of death
• Percentage of subjects with Objective Response [ Time Frame: 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.
• Duration of Response [ Time Frame: 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.
• Percentage of subjects with disease control according to RECIST v.1.1 [ Time Frame: 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
• Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [ Time Frame: 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.
• Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [ Time Frame: 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.
• Serum Carcinoma Antigen 19-9 (CA 19-9) response rate [ Time Frame: 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).

Current Other Pre-specified Outcome Measures (submitted: January 30, 2023)

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score [ Time Frame: Up to approximately 33.5 months (assessed at baseline and end of treatment (EOT)) ]
  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.
• Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score [ Time Frame: 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): 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: EndoTAG-1
  twice weekly
  Other Name: 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 Name: Gemcitabine Hydrochloride

Study Arms

• 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.
  Interventions:

  • Drug: EndoTAG-1
  • Drug: Gemcitabine
• 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.
  Intervention: Drug: Gemcitabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 3, 2019): 218
• Original Estimated Enrollment (submitted: April 19, 2017): 214
• Actual Study Completion Date: October 8, 2021
• Actual Primary Completion Date: July 30, 2021 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Hungary, Israel, Korea, Republic of, Russian Federation, Taiwan, United States
• Removed Location Countries: Czechia, Romania, Spain

Administrative Information

• NCT Number: NCT03126435
• Other Study ID Numbers: CT4006
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: SynCore Biotechnology Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: SynCore Biotechnology Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Li-Tzong Chen, M.D., Ph.D.; National Cheng Kung University Hospital,Tainan, Taiwan, R.O.C

• PRS Account: SynCore Biotechnology Co., Ltd.
• Verification Date: May 2023