Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Age 18 - 75 years
Histologically proven carcinoma,
Documented advanced or metastatic disease not suitable for complete surgical resection
Measurable or evaluable lesions according to RECIST v1.1 criteria
ECOG performance status 0 - 1

Adequate Bone marrow reserves as evidenced by:

Absolute Neutrophil Count (ANC) ≥1.5 x 109/L without the use of hematopoietic growth factors
platelets ≥ 100 x 109/L
hemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
International Normalized Ratio (INR) ≤1.5; aPTT<1.5 x upper normal limit (UNL); EXEMPTION: patients on full anticoagulation therapy due to Venous Thromboembolism (VTE) must have an in-range INR (usually between 2 and 3).

Adequate renal function as evidenced by:

serum creatinine: < 150µmol/l
calculated creatinine clearance > 50ml/min. (recommendation: to be calculated according to the MDRD formula)
Total bilirubin < 1.0 x upper normal limit (UNL)
Normal ECG or ECG without any clinically significant findings
Regular follow-up feasible. A registered patient must be treated and followed at the participating center.
Able to understand and sign an informed consent
No contraindication to any study drugs
Registration in a national health care system (CMU included for France). NB.: prior exposure to irinotecan is allowed, except for irinotecan-refractory patients (i.e. exclusion criteria)

Exclusion Criteria:

Active central nervous system metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease)
Bone-only disease
Clinically significant gastrointestinal (GI) disorder including hepatic disorders, bleeding, inflammation, GI obstruction, or diarrhea > grade 1
Patients refractory to irinotecan (i.e. prior exposure to irinotecan-based therapy with progressive disease as best response)
Known Dose Limiting Toxicity (DLT) responses to irinotecan
Patients known to be homozygous for UGT1A1 *28
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
Prior exposure to MM-398
Known hypersensitivity to any of the components of MM-398, or other liposomal products

Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease

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
Chronic inflammatory bowel disease and/or bowel obstruction
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
Prior chemotherapy administered within 3 weeks, or within a time interval less than at least 5 half-lives of the agent, whichever is longer, prior to the first scheduled day of dosing in this study
Uncontrolled hypertension (defined as persistent systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy
Received radiation therapy in the last 14 days
Major surgery or traumatic injury within the last 28 days
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 including tutelage and guardianship
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 reliable method of birth control, during the study and for 6 months following the last dose of study drug.
Concomitant administrations use with St John Worth, or CYP3A4 inducing anticonvulsants (phenytoin, Phenobarbital, carbamazepine), ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem and verapamil
Concomitant administration of live attenuated virus vaccine such as yellow fever vaccine
Known dihydropyrimidine dehydrogenase (DPD) deficiency
Known active hepatitis B or C and/or active or chronic human immunodeficiency virus (HIV)