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

Phase 3

Completed

• Conditions: Metastatic Pancreas Cancer; Pancreatic Adenocarcinoma; Locally Advanced Pancreatic Cancer
• Interventions: Drug: Gemcitabine; Drug: EndoTAG-1

• Registration Number: NCT03126435
• Lead Sponsor: SynCore Biotechnology Co., Ltd.

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 Timeline

• Study First Submitted: 2017-04-19
• Study First Submitted QC: 2017-04-19
• Study First Posted: 2017-04-24
• Study Start: 2018-10-16
• Primary Completion: 2021-07-30
• Study Completion: 2021-10-08
• Results First Submitted: 2022-11-07
• Results First Submitted QC: 2023-03-01
• Results First Posted: 2023-03-24
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-05
• Last Update Posted: 2023-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 218

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gemcitabine Monotherapy	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.
EndoTAG-1 and Gemcitabine	EndoTAG-1	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.
EndoTAG-1 and Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	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	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	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	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	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.

Trial Locations

Locations (68)

Compassionate Cancer Care Medical Group, Inc; 🇺🇸 Corona, California, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

John B. Amos Cancer Center / IACT Health; 🇺🇸 Columbus, Georgia, United States

Orchard Healthcare Research (OHR) Inc.; 🇺🇸 Skokie, Illinois, United States

Investigator Clinical Research Centers of Indiana; 🇺🇸 Indianapolis, Indiana, United States

Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center); 🇺🇸 Topeka, Kansas, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

North Mississippi Hematology & Oncology Associates, Ltd.; 🇺🇸 Tupelo, Mississippi, United States

Southeast Nebraska Cancer Center (SNCC) - Central Clinic - Main Clinic; 🇺🇸 Lincoln, Nebraska, United States

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