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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01451632
Recruitment Status : Completed
First Posted : October 13, 2011
Results First Posted : September 8, 2016
Last Update Posted : September 8, 2016
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Merrimack Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE October 7, 2011
First Posted Date  ICMJE October 13, 2011
Results First Submitted Date  ICMJE July 12, 2016
Results First Posted Date  ICMJE September 8, 2016
Last Update Posted Date September 8, 2016
Study Start Date  ICMJE October 2011
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
  • 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 ]
    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 ]
    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 ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2011)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
  • 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 ]
    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 ]
    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 ]
    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 ]
    Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers
Official Title  ICMJE A Phase 1 Study of MM-121 in Combination With Cetuximab and Irinotecan in Patients With Advanced Cancers
Brief 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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Cancer
  • Squamous Cell Head and Neck Cancer
  • Non-small Cell Lung Cancer
  • Triple Negative Breast Cancer
  • Other Tumors With EGFR Dependence
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 20, 2013)
48
Original Estimated Enrollment  ICMJE
 (submitted: October 11, 2011)
45
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01451632
Other Study ID Numbers  ICMJE MM-121-05-01-05 (TCD11696)
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Merrimack Pharmaceuticals
Study Sponsor  ICMJE Merrimack Pharmaceuticals
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Victor Moyo, MD Merrimack Pharmaceuticals
PRS Account Merrimack Pharmaceuticals
Verification Date September 2016

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