Clinical Trials /

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

NCT02785068

Description:

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

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MM-151-06-12-04
  • NCT ID: NCT02785068

Trial Conditions

  • Colorectal Cancer

Trial Interventions

DrugSynonymsArms
MM-151Phase 1b/2a
nal-IRIMM-398OnivydePhase 1b/2a
Leucovorinfolinic acidPhase 1b/2a
5-FUfluorouracilPhase 1b/2a

Trial Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b/2aExperimentalPhase 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.
  • MM-151
  • nal-IRI
  • Leucovorin
  • 5-FU

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:Yes
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:Yes
Description: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.
Measure: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
Safety Issue:No
Description:
Measure: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
Safety Issue:No
Description:
Measure:Objective response based on RECIST
Time Frame:2 years
Safety Issue:No
Description:
Measure:Measure pre-treatment and on-treatment levels of EGFR ligands
Time Frame:2 years
Safety Issue:No
Description:
Measure:Presence of anti-drug antibodies will be assessed
Time Frame:2 years
Safety Issue:No
Description:

Trial Keywords

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