Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer

A Phase 1 Study Combining MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer

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

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: MM-151; Drug: nal-IRI; Drug: Leucovorin; Drug: 5-FU

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: MM-151; Oligoclonal antibody; Drug: nal-IRI; Nanoliposomal irinotecan; Other Names: Onivyde; MM-398; Drug: Leucovorin; folinic acid; Other Names: folinic acid; Drug: 5-FU; Chemotherapy; Other Names: fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	2 years
The PK parameters of MM-151 and nal-IRI will be described per Cmax		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		Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1
Objective response based on RECIST		2 years
Measure pre-treatment and on-treatment levels of EGFR ligands		2 years
Presence of anti-drug antibodies will be assessed		2 years

Collaborators and Investigators

• Sponsor: Merrimack Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Cancer; EGFR; Phase I; Oncology; Metastatic Colorectal Cancer; EGFR Inhibitor; RAS/RAF Wild-Type; Nal-IRI; Oligoclonal Antibody; Nanoliposome; Nanoliposomal Irinotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin
• Other Study ID Numbers: MM-151-06-12-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No