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

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01451632
First received: October 7, 2011
Last updated: September 6, 2016
Last verified: September 2016

October 7, 2011
September 6, 2016
October 2011
November 2013   (final data collection date for primary outcome measure)
  • 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 [ Time Frame: From date of first dose to 30 days after termination, the longest 48.1 weeks ] [ Designated as safety issue: Yes ]
    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.
  • 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 [ Time Frame: From date of first dose to 30 days after termination, the longest 48.1 weeks ] [ Designated as safety issue: Yes ]

    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

  • 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 [ Time Frame: From date of first dose to 30 days after termination, the longest 48.1 weeks ] [ Designated as safety issue: Yes ]

    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

Number of dose limiting toxicity (DLT) events with MM-121 plus cetuximab and the MM-121 plus cetuximab plus irinotecan combination [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01451632 on ClinicalTrials.gov Archive Site
  • Objective Response Rate [ Time Frame: Patients were assessed for objective response from time of first dose through treatment termination, the longest treatment duration being 48.1 weeks ] [ Designated as safety issue: No ]
    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.
  • Pharmacokinetics [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)
  • Pharmacokinetic Parameters of MM-121 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)
  • Immunogenicity [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
Not Provided
Not Provided
Not Provided
 
A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers
A Phase 1 Study of MM-121 in Combination With Cetuximab and Irinotecan in Patients With Advanced Cancers
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.
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.
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Colorectal Cancer
  • Squamous Cell Head and Neck Cancer
  • Non-small Cell Lung Cancer
  • Triple Negative Breast Cancer
  • Other Tumors With EGFR Dependence
  • Drug: MM-121
    escalating doses MM-121 IV QW
    Other Name: Seribantumab, SAR256212
  • Drug: Irinotecan
    180 mg/m2 IV Q2W
    Other Name: Camptosar
  • Drug: Cetuximab
    escalating doses cetuximab IV QW
    Other Name: Erbitux
  • Experimental: Part 1: MM-121 + cetuximab
    increasing doses of weekly MM-121 + weekly cetuximab
    Interventions:
    • Drug: MM-121
    • Drug: Cetuximab
  • Experimental: Part 2: MM-121 + cetuximab + irinotecan
    increasing doses of irinotecan + the Recommended Phase 2 Dose/Maximum Tolerated Dose (RP2D/MTD) of MM121 + cetuximab as determined in Part 1
    Interventions:
    • Drug: MM-121
    • Drug: Irinotecan
    • Drug: Cetuximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
June 2014
November 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01451632
MM-121-05-01-05 (TCD11696)
No
No
Not Provided
Merrimack Pharmaceuticals
Merrimack Pharmaceuticals
Sanofi
Study Director: Victor Moyo, MD Merrimack Pharmaceuticals
Merrimack Pharmaceuticals
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP