A randomized Phase 2 study of nal-IRI-containing regimens for untreated metastatic pancreatic cancer.

Phase 1

Conditions: Previously Untreated, Metastatic Pancreatic Adenocarcinoma
MedDRA version: 19.0Level: LLTClassification code 10033599Term: Pancreatic adenocarcinoma metastaticSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-003086-28-ES

Lead Sponsor: Merrimack Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 168

Inclusion Criteria

a) Pathologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting.
? Part 1: unresectable, locally advanced or metastatic disease is allowed, diagnosed within 6 weeks prior to enrollment
? Part 2: must have metastatic disease diagnosed within 6 weeks prior to randomization; locally advanced disease is not allowed
b) Measurable or non-measurable disease as defined by RECIST v1.1
c) ECOG performance status of 0 or 1
d) Adequate biological parameters as evidenced by the following blood counts:
? ANC > 1,500 cells/µl without the use of hematopoietic growth factors,
? Platelet count > 100,000 cells/µl, and
? Hemoglobin > 9 g/dL
e) Adequate hepatic function as evidenced by:
? Serum total bilirubin = ULN (biliary drainage is allowed for biliary obstruction), and? AST and ALT = 2.5 x ULN (= 5 x ULN is acceptable if liver metastases are present)
f) Adequate renal function as evidenced by serum creatinine = 1.5 x ULN, and calculated clearance =60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal value. Actual body weight should be used for calculating creatinine clearance using the Cockcroft-Gault Equation (CreatClear = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72); for patients with body mass index (BMI) >30 kg/m2, lean body weight should be used instead.
g) Normal ECG or ECG without any clinically significant findings
h) Recovered from the effects of any prior surgery or radiotherapy
i) = 18 years of age
j) Agreeable to submit unstained archived tumor tissue for analysis, if available
k) Able to understand and sign an informed consent (or have a legal representative who is able to do so)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 158
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy (note: placement of biliary stent is allowed)
b) Prior treatment of pancreatic cancer with cytotoxic doses of chemotherapy (patients receiving prior treatment with chemotherapy as a radiation sensitizer are eligible if = 6 months has elapsed from completion of therapy)
c) Uncontrolled CNS metastases (patients who require steroids should be on a stable or decreasing dose)
d) Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea > grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction
e) History of any second malignancy in the last 3 years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years.
f) Known hypersensitivity to any of the components of nal-IRI, other liposomal products, or any components of 5-FU, leucovorin or oxaliplatin
g) Known hypersensitivity to any of the components of nab-paclitaxel or gemcitabine (Part 2 only)
h) Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including:
? Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion
? NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
? Known historical or active infection with HIV, hepatitis B, or hepatitis C
i) Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator’s opinion might compromise the patient’s participation in the trial or affect the study outcome
j) Use of strong CYP3A4 inhibitors or inducers, or presence of any other contraindications for irinotecan
k) Presence of any contraindications for 5-FU, leucovorin, or oxaliplatin
l) Use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for nab-paclitaxel or gemcitabine (Part 2 only)1
m) Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
n) Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test. Both male and female patients of reproductive potential must agree to use a highly effective method of birth control, during the study and for 4 months following the last dose of study drug.