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

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.

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)