Clinical trial NCT02785068: Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer
Official title: A Phase 1 Study Combining MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: Phase I
Cancer
EGFR
Metastatic Colorectal Cancer
Oncology
RAS/RAF Wild-Type
Nal-IRI
EGFR Inhibitor
Oligoclonal Antibody
Nanoliposome
Nanoliposomal Irinotecan
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-05-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase 1b/2a study evaluating the combination of MM-151 + nal-IRI + 5-FU + Leucovorin in RAS/RAF wild-type Metastatic Colorectal Cancer.

Detailed description: Part 1: Patients will be enrolled to determine the maximum tolerated dose, safety and tolerability of MM-151 + nal-IRI + 5-FU + LV in patients with mCRC that are RAS/RAF wild-type.

Part 2: Patients will be enrolled at the maximum tolerated dose of MM-151 in combination with nal-IRI + 5-FU + LV to characterize initial efficacy in conjunction with levels of irinotecan and SN-38 measured in tissue.

Eligibility criteria: Inclusion Criteria:

* Patients must be greater than 18 years of age
* Patients must be able to provide informed consent
* Patients must have KRAS/NRAS/BRAF wild-type colorectal cancer
* Willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 120 days following the last dose of any study therapy). This applies to women of childbearing potential as well as fertile men and their partners

Exclusion Criteria:

* Patients who have had previous pelvic radiation treatment
* Patients who are pregnant or lactating
* Patients who have untreated (primary) or uncontrolled Central Nervous System (CNS) (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
* 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 who have received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days and bevacizumab within 28 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of the study treatment

Primary outcomes:
measure: To find the phase II dose of MM-151 based on safety and tolerability of MM-151 + nal-IRI + 5-FU + Leucovorin that will be assessed through evaluation of dose limiting toxicity reporting.
timeFrame: The DLT timeframe is from date of first dose up until 42 days after that date
measure: To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue
timeFrame: 2 years
Secondary outcomes:
measure: The number of participants with adverse events (AE) related to treatment with MM-151 + nal-IRI + 5-FU + leucovorin, assessed according to NCI CTCAE v4.0
timeFrame: 2 years
measure: The PK parameters of MM-151 and nal-IRI will be described per Cmax
timeFrame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1
measure: The PK parameters of MM-151 and nal-IRI will be described per AUC
timeFrame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1
measure: Objective response based on RECIST
timeFrame: 2 years
measure: Measure pre-treatment and on-treatment levels of EGFR ligands
timeFrame: 2 years
measure: Presence of anti-drug antibodies will be assessed
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
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