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

Colorectal Cancer Clinical Trial

Official title:

A Phase 1 Study Combining MM-151 + Nal-IRI + 5-FU + Leucovorin in RAS/RAF Wild-type Metastatic Colorectal Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02785068
• Other study ID #: MM-151-06-12-04
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: May 11, 2016
• Last updated: January 10, 2017
• Start date: July 2016
• Est. completion date: October 2018

Study information

• Verified date: December 2016
• Source: Merrimack Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• MM-151
Oligoclonal antibody
• nal-IRI
Nanoliposomal irinotecan
• Leucovorin
folinic acid
• 5-FU
Chemotherapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	To correlate disease response according to RECIST with levels of irinotecan and SN-38 in tumor tissue		2 years	No
Secondary	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	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 years	Yes
Secondary	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	No
Secondary	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	No
Secondary	Objective response based on RECIST		2 years	No
Secondary	Measure pre-treatment and on-treatment levels of EGFR ligands		2 years	No
Secondary	Presence of anti-drug antibodies will be assessed		2 years	No