Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer
|ClinicalTrials.gov Identifier: NCT02785068|
Recruitment Status : Withdrawn
First Posted : May 27, 2016
Last Update Posted : January 11, 2017
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: MM-151 Drug: nal-IRI Drug: Leucovorin Drug: 5-FU||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study Combining MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer|
|Study Start Date :||July 2016|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||October 2018|
Experimental: Phase 1b/2a
Phase 1b: Safety Evaluation - MM-151 (weekly dosing) in combination with fixed doses of nal-IRI 70mg/m2 + Leucovorin 400 mg/m2 + 5-FU 2400mg/m2 every two weeks.
Phase 2a: Expansion - MM-151 (Maximum Tolerated Dose or Recommended Phase 2 Dose) in combination with fixed doses of nal-IRI 70mg/m2 + Leucovorin 400 mg/m2 + 5-FU 2400 mg/m2.
Other Name: folinic acid
Other Name: fluorouracil
- 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. [ Time Frame: The DLT timeframe is from date of first dose up until 42 days after that date ]
- To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue [ Time Frame: 2 years ]
- 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 [ Time Frame: 2 years ]
These will be described by abnormalities in hematology, blood chemistry and other laboratory abnormalities, ECG, physical examination, vital signs and other safety parameters.
Frequency, duration and severity of the adverse events according to NCI CTCAE v4.0 will be assessed.
- The PK parameters of MM-151 and nal-IRI will be described per Cmax [ Time Frame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1 ]
- The PK parameters of MM-151 and nal-IRI will be described per AUC [ Time Frame: Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1 ]
- Objective response based on RECIST [ Time Frame: 2 years ]
- Measure pre-treatment and on-treatment levels of EGFR ligands [ Time Frame: 2 years ]
- Presence of anti-drug antibodies will be assessed [ Time Frame: 2 years ]