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

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ClinicalTrials.gov Identifier: NCT02785068
Recruitment Status : Withdrawn
First Posted : May 27, 2016
Last Update Posted : January 11, 2017
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: MM-151 Drug: nal-IRI Drug: Leucovorin Drug: 5-FU Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

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:
  • MM-398
  • Onivyde

Drug: Leucovorin
folinic acid
Other Name: folinic acid

Drug: 5-FU
Other Name: fluorouracil

Primary Outcome Measures :
  1. 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 ]
  2. To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. 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.

  2. 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 ]
  3. 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 ]
  4. Objective response based on RECIST [ Time Frame: 2 years ]
  5. Measure pre-treatment and on-treatment levels of EGFR ligands [ Time Frame: 2 years ]
  6. Presence of anti-drug antibodies will be assessed [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02785068    
Other Study ID Numbers: MM-151-06-12-04
First Posted: May 27, 2016    Key Record Dates
Last Update Posted: January 11, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Merrimack Pharmaceuticals:
Phase I
Metastatic Colorectal Cancer
RAS/RAF Wild-Type
EGFR Inhibitor
Oligoclonal Antibody
Nanoliposomal Irinotecan
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex