ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    MM-151 ONIVYDE
Previous Study | Return to List | Next Study

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Recruitment Status : Withdrawn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

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
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
Chemotherapy
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02785068     History of Changes
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
Cancer
EGFR
Metastatic Colorectal Cancer
Oncology
RAS/RAF Wild-Type
Nal-IRI
EGFR Inhibitor
Oligoclonal Antibody
Nanoliposome
Nanoliposomal Irinotecan

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Levoleucovorin
Folic Acid
Antidotes
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hematinics