Overview

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

Status:
Completed
Trial end date:
2016-12-07
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
GERCOR - Multidisciplinary Oncology Cooperative Group
Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Collaborator:
Merrimack Pharmaceuticals
Treatments:
Bevacizumab
Camptothecin
Irinotecan
Leucovorin
Criteria
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)

Exclusion Criteria:

1. Active central nervous system metastases (indicated by clinical symptoms, cerebral
edema, steroid requirement, or progressive disease)

2. Bone-only disease

3. Clinically significant gastrointestinal (GI) disorder including hepatic disorders,
bleeding, inflammation, GI obstruction, or diarrhea > grade 1

4. Patients refractory to irinotecan (i.e. prior exposure to irinotecan-based therapy
with progressive disease as best response)

5. Known Dose Limiting Toxicity (DLT) responses to irinotecan

6. Patients known to be homozygous for UGT1A1 *28

7. 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

8. Prior exposure to MM-398

9. Known hypersensitivity to any of the components of MM-398, or other liposomal products

10. 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

11. Chronic inflammatory bowel disease and/or bowel obstruction

12. 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

13. 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

14. 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

15. Received radiation therapy in the last 14 days

16. Major surgery or traumatic injury within the last 28 days

17. 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

18. 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.

19. Concomitant administrations use with St John Worth, or CYP3A4 inducing anticonvulsants
(phenytoin, Phenobarbital, carbamazepine), ketoconazole, itraconazole, troleandomycin,
erythromycin, diltiazem and verapamil

20. Concomitant administration of live attenuated virus vaccine such as yellow fever
vaccine

21. Known dihydropyrimidine dehydrogenase (DPD) deficiency

22. Known active hepatitis B or C and/or active or chronic human immunodeficiency virus
(HIV)