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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02785068
Recruitment Status : Withdrawn
First Posted : May 27, 2016
Last Update Posted : January 11, 2017
Sponsor:
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 11, 2016
First Posted Date  ICMJE May 27, 2016
Last Update Posted Date January 11, 2017
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
  • The adverse event profile of MM-151 + nal-IRI + 5-FU + leucovorin [ Time Frame: 2 years ]
  • The PK parameters of MM-151 and nal-IRI will be described per Cmax [ Time Frame: 2 years ]
  • Presence of immunogenicity will be assessed [ Time Frame: 2 years ]
  • Objective response based on RECIST [ Time Frame: 2 years ]
  • Measure pre-treatment and on-treatment levels of EGFR ligands [ Time Frame: 2 years ]
  • The PK parameters of MM-151 and nal-IRI will be described per AUC [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer
Official Title  ICMJE A Phase 1 Study Combining MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • 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
    Chemotherapy
    Other Name: fluorouracil
Study Arms  ICMJE 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.

Interventions:
  • Drug: MM-151
  • Drug: nal-IRI
  • Drug: Leucovorin
  • Drug: 5-FU
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 10, 2017)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2016)
28
Estimated Study Completion Date  ICMJE October 2018
Estimated Primary Completion Date May 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02785068
Other Study ID Numbers  ICMJE MM-151-06-12-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Merrimack Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merrimack Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merrimack Pharmaceuticals
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP