A Dose Escalation Study of MM-398 Plus Irinotecan in Patients With Unresectable Advanced Cancer

NCT02640365 | Completed Phase 1

• 1 other identifier: DOUBLIRI C13-4
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Unresectable Advanced Cancer

Keywords

cancer; GERCOR; unresectable; MM-398; CPT-11; colorectal; non colorectal

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Response Rate (RR)

  tumor responses will be evaluated every 8 weeks after start treatment up to 29 months

• 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

• 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

• 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

Study Arms (1)

GROUP A / GROUP B (two differents cohorts)

EXPERIMENTAL

GROUP A (Patients with unresectable advanced non-colorectal cancer ) - irinotecan + MM-398 dose escalation (3-18 patients) Level 1 : initial DOUBLIRI dose 60/90 (0-3 patients) * MM-398 : 60mg/m² * Irinotecan (CPT-11) : 90mg/m² Level 2: DOUBLIRI dose 80/90 (9 - 18 patients) * MM-398 : 80mg/m² * CPT-11: 90mg/m² Level 3A: DOUBLIRI dose 60/120 (12-18 patients) * MM-398 : 60mg/m² * CPT-11: 120mg/m² Level 3B: DOUBLIRI dose : 80/120 (12-18 patients) * MM-398 : 80mg/m² * CPT-11 : 120 mg/m² GROUP B (Patients with unresectable metastatic colorectal cancer)- LV/5FU-bevacizumab+irinotecan+MM-398 dose Escalation (3-18 patients) same level as group A + LV/5FU - bevacizumab regimen : * Bevacizumab : 5mg/kg(day (d) 1) * Leucovorin (LV) : 400mg/m² (d1) * 5-fluorouracile infusion (5 FU) :2400mg/m² (d1,2)

Drug: MM-398; Drug: Irinotecan; Drug: Leucovorin (LV); Drug: 5-fluorouracile (5-FU); Drug: bevacizumab

Interventions

MM-398 DRUG

unresectable Advanced non-colorectal cancer

Also known as: GROUP A

GROUP A / GROUP B (two differents cohorts)

Irinotecan DRUG

unresectable metastatic colorectal cancer

Also known as: GROUP A

GROUP A / GROUP B (two differents cohorts)

Leucovorin (LV) DRUG

unresectable metastatic colorectal cancer

Also known as: GROUPE B

GROUP A / GROUP B (two differents cohorts)

5-fluorouracile (5-FU) DRUG

unresectable metastatic colorectal cancer

Also known as: GROUPE B

GROUP A / GROUP B (two differents cohorts)

bevacizumab DRUG

unresectable metastatic colorectal cancer

Also known as: GROUPE B

GROUP A / GROUP B (two differents cohorts)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• Merrimack Pharmaceuticals: collaborator

Study Sites (1)

Hôpital Saint Antoine

Paris, 75012, France

Location

MeSH Terms

Conditions

Neoplasms

Interventions

irinotecan sucrosofate; Irinotecan; Leucovorin; Fluorouracil; Bevacizumab

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Benoist Chibaudel, MD

  Franco-British Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 28, 2015
• Study Start: November 18, 2015
• Primary Completion: December 7, 2016
• Study Completion: December 7, 2016
• Last Updated: January 31, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)