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

Primary Purpose

Colorectal Cancer

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

MM-151

nal-IRI

Leucovorin

5-FU

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Phase I, Cancer, EGFR, Metastatic Colorectal Cancer, Oncology, RAS/RAF Wild-Type, Nal-IRI, EGFR Inhibitor, Oligoclonal Antibody, Nanoliposome, Nanoliposomal Irinotecan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phase 1b/2a

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue

Secondary Outcome Measures

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.

The PK parameters of MM-151 and nal-IRI will be described per Cmax

The PK parameters of MM-151 and nal-IRI will be described per AUC

Objective response based on RECIST

Measure pre-treatment and on-treatment levels of EGFR ligands

Presence of anti-drug antibodies will be assessed

Full Information

NCT ID

NCT02785068

First Posted

May 11, 2016

Last Updated

January 10, 2017

Sponsor

Merrimack Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02785068

Brief Title

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

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Withdrawn

Study Start Date

July 2016 (undefined)

Primary Completion Date

May 2018 (Anticipated)

Study Completion Date

October 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merrimack Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

Phase I, Cancer, EGFR, Metastatic Colorectal Cancer, Oncology, RAS/RAF Wild-Type, Nal-IRI, EGFR Inhibitor, Oligoclonal Antibody, Nanoliposome, Nanoliposomal Irinotecan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1b/2a

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

MM-151

Intervention Description

Oligoclonal antibody

Intervention Type

Drug

Intervention Name(s)

nal-IRI

Other Intervention Name(s)

MM-398, Onivyde

Intervention Description

Nanoliposomal irinotecan

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Other Intervention Name(s)

folinic acid

Intervention Description

folinic acid

Intervention Type

Drug

Intervention Name(s)

5-FU

Other Intervention Name(s)

fluorouracil

Intervention Description

Chemotherapy

Primary Outcome Measure Information:

Title

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

Title

To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue

Time Frame

2 years

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

2 years

Title

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

Title

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

Title

Objective response based on RECIST

Time Frame

2 years

Title

Measure pre-treatment and on-treatment levels of EGFR ligands

Time Frame

2 years

Title

Presence of anti-drug antibodies will be assessed

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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