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Unresectable Advanced CancerPhase 1DOUBLIRINCT02640365

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

A Phase 1 study testing MM-398, Irinotecan and Leucovorin (LV) in people with Unresectable Advanced Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Unresectable Advanced Cancer
What is being tested?
MM-398, Irinotecan and Leucovorin (LV)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteFrance
Study dates
18 Nov 2015to 7 Dec 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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)

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

France1 site

  • Hôpital Saint Antoine

    Paris, 75012

Other trials in France

About this study

Official title: A Phase Ib Dose Escalation Study of MM-398 Plus Irinotecan in Patients With Unresectable Advanced Cancer - DOUBLIRI

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.

Read the 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

Being tested
MM-398, Irinotecan, Leucovorin (LV), 5-fluorouracile (5-FU), bevacizumab
Keywords
cancer, GERCOR, unresectable, MM-398, CPT-11, colorectal, non colorectal
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MM-398Drug

    Also called GROUP A

    unresectable Advanced non-colorectal cancer

  • IrinotecanDrug

    Also called GROUP A

    unresectable metastatic colorectal cancer

  • Leucovorin (LV)Drug

    Also called GROUPE B

    unresectable metastatic colorectal cancer

  • 5-fluorouracile (5-FU)Drug

    Also called GROUPE B

    unresectable metastatic colorectal cancer

  • bevacizumabDrug

    Also called GROUPE B

    unresectable metastatic colorectal cancer

  • MM-398Drug

    Also called GROUPE B

    unresectable metastatic colorectal cancer

Study groups in NCT02640365
Study groupRoleWhat they receive
GROUP A / GROUP B (two differents cohorts)ExperimentalGROUP 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)
Receives: Drug: MM-398; Drug: Irinotecan; Drug: Leucovorin (LV); Drug: 5-fluorouracile (5-FU); Drug: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Event (AE)

    Measured: Assessed from study inclusion to 30 days after last dose

  2. Dose Limiting Toxicities (DLT)

    Measured: DLTs will be evaluated during 28-day period following the first dose of study treatment

  3. Maximal tolerated dose (MTD)

    Measured: after the last patient in each cohort up to 28 months

Secondary outcomes (5)

  1. Response Rate (RR)

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

  2. Best overall Response (BOR)

    Measured: BOR is the best response recorded from the inclusion until treatment failure up to 28 months

  3. Overall survival (OS)

    Measured: 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

  4. Progression free survival (PFS)

    Measured: PFS is the time from the date of inclusion to the date of progressive disease or death up to 29 months

  5. Pharmacokinetic of MM-398 plus irinotecan combination therapy

    to determine the levels of MM-398/irinotecan, SN-38 and SN-38G

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2015 (estimated)
  2. Study start18 Nov 2015
  3. Primary completion7 Dec 2016
  4. Study completion7 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02640365
Sponsor's protocol ID
DOUBLIRI C13-4
Acronym
DOUBLIRI
Status last verified
Jan 2017
First submitted
16 Dec 2015
Last updated
31 Jan 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MM-398, Irinotecan and Leucovorin (LV) in people with Unresectable Advanced Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Event (AE) (time frame: Assessed from study inclusion to 30 days after last dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02640365.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2017.

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