Patients with metastatic adenocarcinoma of the pancreas who have not received prior therapy for their metastatic disease MedDRA version: 18.0 Level: LLT Classification code 10033599 Term: Pancreatic adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Interventions
Product Code: MM-141
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: MM-141
Current Sponsor code: MM-141
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Con
Sponsors
Merrimack Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for All Patients a) Metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are not eligible. b) Patient must have received no prior radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior systemic treatment in the adjuvant setting is only allowed if administered as a radiation sensitizer and if it was provided > 6 months prior to enrollment onto this study. c) Candidates to receive nab-paclitaxel and gemcitabine per the label of the combination d) ? 18 years of age e) Able to provide informed consent, or have a legal representative able and willing to do so. Additional Inclusion Criteria for Part 1 and the Interventional Group: a) High serum levels of free IGF-1, defined as ? 0.390 ng/ml b) ECOG Performance Status (PS) of 0,1 c) Adequate bone marrow reserve as evidenced by: ? ANC > 1,500/?l ? Platelet count > 100,000/?l ? Hemoglobin > 9 g/dL d) Adequate renal function as evidenced by a serum/plasma creatinine 3 g/dL g) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5 x ULN (?5 x ULN is acceptable if liver metastases are present) h) Significant or symptomatic amounts of ascites should be drained, and pain symptoms should be stable prior to Day 1 i) Women of childbearing potential must be willing to abstain from sexual intercourse or to use a highly effective form of contraception during the study and for 90 days following the last dose of study drug(s). Fertile men and their partners must be willing to abstain from sexual intercourse or to use an highly effective form of contraception during the study and for 6 months following the last dose of study drug(s), in accordance with the label requirements for nab-paclitaxel and gemcitabine. Male patients should seek advice regarding cryoconservation of sperm prior to treatment with nab-paclitaxel/gemcitabine because of the posibility of infertility. Additional inclusion criteria for the interventional group only ?must have: a) Available recent tumor specimen, collected after all prior adjuvant treatment or at the time of initial metastatic diagnosis, submitted to the central lab OR b) Disease must be amenable to biopsy, and patient must be appropriate candidate for a biopsy per the Investigator?s judgment. ? b.1. Patient must be willing to undergo the pre-treatment biopsy ? b.2. Coagulation profile (INR and aPTT) within the institutional guidelines prior to the pre-treatment biopsy ? Measureable disease in accordance with RECIST v1.1 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 144 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: a) Pregnant or lactating b) Patients who only present with localized disease c) Presence of an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing, which in the investigator?s opinion might compromise the patient?s participation in the trial or affect the study outcome. If the fever and active infection have resolved prior to randomization, the patient will be eligible. At the discretion of the investigator, patients with tumor fever may be enrolled d) Patients with CNS malignancies (primary or metastatic) are excluded. e) History of any malignancy in the last 3 years. Subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 3 years. f) Known hypersensitivity to the components of MM-141, an anti-ErbB3 monoclonal antibody, an anti-IGF-1R monoclonal antibody, or who have had Grade 3-4 hypersensitivity reactions to human monoclonal antibodies g) Prior treatment with any kind of IGF-1R or ErbB3 target agents at any time prior to enrolling into this study h) Known history of allergy or hypersensitivity to nab-paclitaxel, gemcitabine or their excipients i) Known hypersensitivity against polysorbate (Tween) 80 or arginine j) Clinically significant cardiac disease, including: NYHA Class III or IV congestive heart failure, unstable angina, acute myocardial infarction within six months of planned first dose, arrhythmia requiring therapy (including torsades de pointes, with the exception of extra systoles, minor conduction abnormalities, or controlled and well treated chronic atrial fibrillation) k) Any episode of uncontrolled bleeding within the last 4 months. l) Patient has known historical or active infection with HIV, hepatitis B, or hepatitis C m) History of connective tissue disorders (e.g. lupus, scleroderma, arteritis nodosa) n) History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis o) History of peripheral artery disease (e.g. claudication, Leo Buerger?s disease) p) Use of strong CYP3A4 and/or CYP2C8 inhibitors or inducers q) Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Part 1 ? describe PK profile of a fixed-dose regimen of MM-141 in patients with metastatic pancreatic cancer and high free IGF-1 Part 2 ? evaluate if combination with MM-141 is more effective than nab-paclitaxel and gemcitabine alone ? describe safety and tolerability of the combination of MM-141 plus nab-paclitaxel and gemcitabine ? compare overal survival (OS) between treatment arms in patients whose pretreatment tumor samples are positive for HRG Exploratory Objectives ? OS results from observational group will be displayed using Kaplan Meier methods. Results will be compared against OS results from the interventional group. ? further characterize PK profile of MM-141 when used in combination in patients with metastatic pancreatic cancer and high serum free IGF-1 ? describe changes in CA19-9 and their potential correlation with clinical outcome ? evaluate if pre-specified mechanistic biomarkers, from tumor tissue and/or blood samples, correlate with clinical outcomes;Main Objective: Part 1 ? To characterize safety and tolerability of a fixed-dose regimen of MM-141 in combination with nab-paclitaxel and gemcitabine Part 2 ? To determine whether the combination of MM-141 plus nab-paclitaxel and gemcitabine is more effective than nab-paclitaxel and gemcitabine alone based on Progression Free Survival (PFS) in front-line metastatic pancreatic cancer patients with: o High serum levels of free IGF-1 o High serum levels of free IGF-1 and pre-treatment tissue samples positive for Heregulin (HRG);Primary end point(s): Progression-free survival, based on Investigator assessment. It will be assessed in two patient populations: patients with high serum levels of free IGF-1 and patients with high serum levels of free IGF-1 and pre-treatment tissue samples positive for HRG.;Timepoint(s) of evaluation of this end point: PFS defined as the time from randomization to the first documented radiographical progression of disease using RECIST 1.1, or death f | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS).;Timepoint(s) of evaluation of this end point: the time from the date of randomization until the date of death from any cause [ Time Frame: Approximately 2.5 years ]. | — |
Countries
Belgium, Canada, Germany, Poland, Spain, United Kingdom, United States
Contacts
Public ContactManuel Hidalgo
.
Outcome results
None listed