EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX
Condition: Metastatic Pancreas Cancer; Locally Advanced Pancreatic Cancer; Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Intervention: EndoTAG-1; Gemcitabine
Intervention description: twice weekly; once weekly
Intervention MeSH terms: Gemcitabine; Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 218.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: FOLFIRINOX; 5-Fluorouracil; folinic acid; irinotecan; oxaliplatin; Gemcitabine

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.
    

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)