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

NCT02785068 | Withdrawn Phase 1

• 1 other identifier: MM-151-06-12-04
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  2 years

Secondary Outcomes (6)

• 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

  2 years

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

  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

  Priming Phase Day 1, Priming Phase Day 8, C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C2D17, C2D22, C3D1, C5D1

• Objective response based on RECIST

  2 years

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

  2 years

Study Arms (1)

Phase 1b/2a

EXPERIMENTAL

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; Drug: nal-IRI; Drug: Leucovorin; Drug: 5-FU

Interventions

MM-151 DRUG

Oligoclonal antibody

Phase 1b/2a

nal-IRI DRUG

Nanoliposomal irinotecan

Also known as: MM-398, Onivyde

Phase 1b/2a

Leucovorin DRUG

folinic acid

Also known as: folinic acid

Phase 1b/2a

5-FU DRUG

Chemotherapy

Also known as: fluorouracil

Phase 1b/2a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merrimack Pharmaceuticals: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

MM-151; irinotecan sucrosofate; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 27, 2016
• Study Start: July 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: October 1, 2018
• Last Updated: January 11, 2017

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share