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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Metastatic Pancreas Cancer, Locally Advanced Pancreatic Cancer, Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: EndoTAG-1
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Written informed consent Histologically or cytologically confirmed adenocarcinoma of the pancreas Metastatic or locally advanced disease that is considered unresectable Measurable / assessable disease according to RECIST v.1.1 Documented disease progression on first line FOLFIRINOX Negative pregnancy test 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). ECOG performance status 0 or 1 Exclusion Criteria: Cardiovascular disease, New York Heart Association (NYHA) III or IV History of severe supraventricular or ventricular arrhythmia History of coagulation or bleeding disorder History of acute myocardial infarction within 6 months before randomization History of congestive heart failure Acute or chronic inflammation (autoimmune or infectious) Significant active/unstable non-malignant disease likely to interfere with study assessments Laboratory tests (hematology, chemistry) outside specified limits: WBC ≤ 3 x 10³/mm³ ANC ≤ 1.5 x 10³/mm³ Platelets ≤ 100.000/mm³ Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) aPTT > 1.5 x ULN Serum creatinine > 2.0 mg/dl (> 176.8 μmol/l) AST and/or ALT > 2.5 x ULN; for patients with significant liver metastasis AST and/or ALT > 5 x ULN Alkaline phosphatase > 2.5 x ULN Total bilirubin > 2 x ULN Albumin < 2.5 g/dL Clinically significant ascites 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. Any radiotherapy for pancreatic adenocarcinoma before enrollment except for treatment of bone metastases if target lesions are not included in the irradiated field Major surgery < 4 weeks prior to enrollment Pregnant or nursing Investigational medicinal product < 4 weeks of enrollment Documented HIV history 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. Known hypersensitivity to any component of the EndoTAG-1 and/or gemcitabine formulations 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 Vulnerable populations (e.g. subjects unable to understand and give voluntary informed consent)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EndoTAG-1 and Gemcitabine<br>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<br>* twice weekly<br>* Other names: 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<br>* once weekly<br>* Other names: Gemcitabine Hydrochloride;|
| Active Comparator: Gemcitabine Monotherapy<br>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<br>* once weekly<br>* Other names: Gemcitabine Hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | 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. | From randomization to death from any cause or last day known to be alive, up to approximately 33.5 months (assessed continuously during treatment) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FOLFIRINOX, 5-Fluorouracil, folinic acid, irinotecan, oxaliplatin, Gemcitabine