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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
  Purpose
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.

Condition Intervention Phase
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
Drug: Irinotecan
Drug: Cetuximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of MM-121 in Combination With Cetuximab and Irinotecan in Patients With Advanced Cancers

Resource links provided by NLM:


Further study details as provided by Merrimack Pharmaceuticals:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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).


Enrollment: 48
Study Start Date: October 2011
Study Completion Date: June 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: MM-121 + cetuximab
increasing doses of weekly MM-121 + weekly cetuximab
Drug: MM-121
escalating doses MM-121 IV QW
Other Name: Seribantumab, SAR256212
Drug: Cetuximab
escalating doses cetuximab IV QW
Other Name: Erbitux
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
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451632

Locations
United States, California
San Francisco, California, United States, 94115
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Merrimack Pharmaceuticals
Sanofi
Investigators
Study Director: Victor Moyo, MD Merrimack Pharmaceuticals
  More Information

Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01451632     History of Changes
Other Study ID Numbers: MM-121-05-01-05 (TCD11696) 
Study First Received: October 7, 2011
Results First Received: July 12, 2016
Last Updated: September 6, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Merrimack Pharmaceuticals:
Metastatic Colorectal cancer
Kras wild-type
Squamous cell head and neck cancer
Non-small cell lung cancer
Triple negative breast cancer
EGFR
ErbB3
MM-121
Cetuximab
Irinotecan

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Head and Neck Neoplasms
Triple Negative Breast Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Irinotecan
Camptothecin
Cetuximab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 08, 2016