Unresectable Advanced Cancer
Conditions
Keywords
cancer, GERCOR, unresectable, MM-398, CPT-11, colorectal, non colorectal
Brief summary
MM-398 (also known as PEP02) is nanoliposomal encapsulated irinotecan: the liposomal formulation is designed to extend plasma circulation and to increase accumulation in the tumor through the enhanced permeability and retention (EPR) effect. This study introduces a new concept of combining free and nanoliposomal drugs.
Detailed description
This is a dose-finding and therapeutic exploratory phase Ib multi-center, open label study of MM-398 plus irinotecan in two different settings: * Group A : patients with unresectable advanced non-colorectal cancer who should receive only MM-398 and irinotecan * Group B : patients with unresectable metastatic colorectal cancer who should receive MM-398 and irinotecan combined with leucovorin, 5-fluorouracil and bevacizumab. These groups will be enrolling in parallel. Pharmacokinetic and biomarker sampling will also be performed. There are three periods to this study : Screening period (up to -28d): patients undergo screening assessments to determine the eligibility for the study MM-398 treatment period (C1D1 until safety evaluation/progression): patients receive treatment every 2 weeks and undergo biopsies and other required assessments. The treatment period is divided into a maximum of 3 dose levels Follow up period: patients will be followed-up 30 days after their last dose of MM-398 for final safety assessments, and every 2 months thereafter for overall survival follow-up
Interventions
DRUGMM-398
unresectable Advanced non-colorectal cancer
DRUGIrinotecan
unresectable metastatic colorectal cancer
DRUGLeucovorin (LV)
unresectable metastatic colorectal cancer
DRUG5-fluorouracile (5-FU)
unresectable metastatic colorectal cancer
DRUGbevacizumab
unresectable metastatic colorectal cancer
Sponsors
Merrimack Pharmaceuticals
GERCOR - Multidisciplinary Oncology Cooperative Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 - 75 years 2. Histologically proven carcinoma, 3. Documented advanced or metastatic disease not suitable for complete surgical resection 4. Measurable or evaluable lesions according to RECIST v1.1 criteria 5. ECOG performance status 0 - 1 6. 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) 7. 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). 8. Adequate renal function as evidenced by: * serum creatinine: \< 150µmol/l * calculated creatinine clearance \> 50ml/min. (recommendation: to be calculated according to the MDRD formula) 9. Total bilirubin \< 1.0 x upper normal limit (UNL) 10. Normal ECG or ECG without any clinically significant findings 11. Regular follow-up feasible. A registered patient must be treated and followed at the participating center. 12. Able to understand and sign an informed consent 13. No contraindication to any study drugs 14. 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
)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Event (AE) | Assessed from study inclusion to 30 days after last dose |
| Dose Limiting Toxicities (DLT) | DLTs will be evaluated during 28-day period following the first dose of study treatment |
| Maximal tolerated dose (MTD) | after the last patient in each cohort up to 28 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | PFS is the time from the date of inclusion to the date of progressive disease or death up to 29 months | — |
| Response Rate (RR) | tumor responses will be evaluated every 8 weeks after start treatment up to 29 months | — |
| Pharmacokinetic of MM-398 plus irinotecan combination therapy | cycle 1 Day 1 (1 cycle every 2 weeks) at Hour (H) 0, H+1, H+2.5, H+4.5, H+6.5, H+26.5, Day 3, Day 8, Day 15 and 30 days after the last dose of treatment | to determine the levels of MM-398/irinotecan, SN-38 and SN-38G |
| Best overall Response (BOR) | BOR is the best response recorded from the inclusion until treatment failure up to 28 months | — |
| Overall survival (OS) | assessed from the date of inclusion to the date of patient death, due to any cause or to the last date the patient was known to be alive, up to 29 months | — |
Countries
France
Outcome results
None listed