A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers

Colorectal Cancer Clinical Trial

Official title:

A Phase 1 Study of MM-121 in Combination With Cetuximab and Irinotecan in Patients With Advanced Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451632
• Other study ID #: MM-121-05-01-05 (TCD11696)
• Status: Completed
• Phase: Phase 1
• First received: October 7, 2011
• Last updated: September 6, 2016
• Start date: October 2011
• Est. completion date: June 2014

Study information

• Verified date: September 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

The purpose of this study was to evaluate the safety and tolerability of escalating doses of the MM-121 plus cetuximab and the MM-121 plus cetuximab plus irinotecan combination.

Description:

This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 plus cetuximab plus irinotecan. The study assessed the safety, tolerability, and pharmacokinetics of MM-121, cetuximab and irinotecan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• No standard options remaining

• Adequate liver and kidney functions

• 18 years of age or above

Exclusion Criteria:

• History of any secondary active cancer in the last 3 years.

• Pregnant or breast feeding

• History of severe allergic reactions or contraindications to cetuximab or irinotecan

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Head and Neck Neoplasms
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Other Tumors With EGFR Dependence
• Squamous Cell Head and Neck Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• MM-121
escalating doses MM-121 IV QW
• Irinotecan
180 mg/m2 IV Q2W
• Cetuximab
escalating doses cetuximab IV QW

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals	Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Cetuximab and the MM-121 Plus Cetuximab Plus Irinotecan Combination	To establish the safety of escalating doses of MM-121 in combination with cetuximab or in combination with cetuximab and irinotecan in order to determine the recommended phase 2 dose.. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.	From date of first dose to 30 days after termination, the longest 48.1 weeks	Yes
Primary	To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s) (Via Recording of Maximum Tolerated Dose (MTD)): MM-121 Doses	Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD; Part 1: Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW; Part 2: Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2	From date of first dose to 30 days after termination, the longest 48.1 weeks	Yes
Primary	To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s): Cetuximab and Irinotecan	Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD; Part 1: Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW; Part 2: Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2	From date of first dose to 30 days after termination, the longest 48.1 weeks	Yes
Secondary	Objective Response Rate	To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR.	Patients were assessed for objective response from time of first dose through treatment termination, the longest treatment duration being 48.1 weeks	No
Secondary	Pharmacokinetics	Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)	Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121	No
Secondary	Pharmacokinetic Parameters of MM-121	Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the AUClast. Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)	Collections taken for all patients at Cycle 1, Week 1 at pre-infusion, at the end of the infusion, and 2.5, 4, 6 and 24 hours after starting the infusion of MM-121	No
Secondary	Immunogenicity	Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).	Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 48.1 weeks, and a collection was made post-infusion in any case of infusion reaction	No