| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with metastatic adenocarcinoma of the pancreas who have not received prior therapy for their metastatic disease |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033599 |
| E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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) |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior systemic treatment in the adjuvant setting (either alone and/or as a radiosensitizer) is only allowed if administered ≥ 6 months prior to enrollment onto this study. Prior radiotherapy to metastatic lesions will be considered on a case by case basis after discussion with the sponsor.
c) Candidates to receive nab-paclitaxel and gemcitabine per the label of the combination
d) ≥ 18 years of age
e) Must provide informed consent, or have a legal representative able and willing to do so in accordance with the local regulatory definitions and requirements, in cases where the patient does not have the capacity to sign the informed consent form.
Additional Inclusion Criteria for Part 1 and the Interventional Group:
a) High serum levels of free IGF-1
b) ECOG Performance Status (PS) of 0,1
c) Adequate bone marrow reserve as evidenced by:
• ANC > 1,500/μl
• Platelet count > 100,000/μl
• Hemoglobin > 9 g/dL
d) Adequate renal function as evidenced by a serum/plasma creatinine < 1.5 x ULN
e) Serum/plasma total bilirubin within normal range for the institution
f) Serum/plasma albumin levels >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 drugs. Fertile men and their partners must be willing to abstain from sexual intercourse or to use a 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 possibility of infertility.
• Additional Inclusion Criteria for the Interventional Group Only:
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 |
|
| E.4 | Principal 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
r) Patients housed in an institution following a regulatory or judicial order, in accordance with the local regulatory definitions and requirements |
|
| E.5 End points |
| E.5.1 | 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. |
|
| E.5.1.1 | 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 from any cause, whichever comes first. [Time Frame: Approximately 2 years] |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | 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]. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| Canada |
| Germany |
| Poland |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The trial will end approximately one year after 101 deaths have been reported or the trial is terminated by the Sponsor. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
