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Trial record 1 of 1 for:    NCT01447225
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Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01447225
First received: October 3, 2011
Last updated: September 13, 2016
Last verified: September 2016

October 3, 2011
September 13, 2016
October 2011
November 2013   (final data collection date for primary outcome measure)
  • To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting
  • To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]

    Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

    Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3

  • To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]

    Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

    Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8

  • To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]

    Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula

    Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

    Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1

  • To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]

    Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

    Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1

  • To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]

    Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

    Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3

  • To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies [ Time Frame: From date of first dose to 30 days after termination, the longest 88.1 weeks ] [ Designated as safety issue: Yes ]
    To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies 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 be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
Number of dose limiting toxicities (DLTs) within a cohort [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01447225 on ClinicalTrials.gov Archive Site
  • Objective Response Rate [ Time Frame: patients were assessed for response during their time on study, the longest of which was 88.1 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 at Cycle 1, Week 1 for all patients at start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle 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).
  • Pharmacokinetics (AUClast) [ Time Frame: Collections taken at Cycle 1, Week 1 for all patients at the start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion ] [ Designated as safety issue: No ]
    Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle 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 88.1 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
 
Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors
A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors
To evaluate the safety and tolerability of escalating doses of MM-121 + certain anticancer therapies
This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 in combination with certain anticancer therapies. The dose-escalation portion of the study employed a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of MM-121 administered weekly in combination with certain anticancer therapies in patients with advanced/recurrent cancer. Doses of MM-121 and/or the anticancer therapy were escalated until either the MTD is identified or the combination was shown to be tolerable at the highest planned doses.
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumors
  • Drug: MM-121
    MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV
    Other Name: Seribantumab, SAR256212
  • Drug: Carboplatin
    administered at AUC 6
  • Drug: Pemetrexed
    administered IV at 500 mg/m2
    Other Name: ALIMTA
  • Drug: Cabazitaxel
    administered IV at 20 mg/m2 or 25 mg/m2
    Other Name: Jevtana
  • Drug: Gemcitabine
    administered IV at 1000 mg/m2 or 1250 mg/m2
    Other Name: Gemzar
  • Experimental: MM-121 plus Gemcitabine
    escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle
    Interventions:
    • Drug: MM-121
    • Drug: Gemcitabine
  • Experimental: MM-121 plus Carboplatin
    carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle
    Interventions:
    • Drug: MM-121
    • Drug: Carboplatin
  • Experimental: MM-121 plus Pemetrexed
    pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle
    Interventions:
    • Drug: MM-121
    • Drug: Pemetrexed
  • Experimental: MM-121 plus Cabazitaxel
    escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle
    Interventions:
    • Drug: MM-121
    • Drug: Cabazitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
43
January 2014
November 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Advanced-stage solid tumors
  • ≥ 18 years of age
  • Adequate liver and kidney function

Exclusion Criteria:

  • Any other active malignancy
  • No known HIV, Hepatitis C or B
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France
 
NCT01447225
MM-121-06-01-06 (TCD11694)
No
Not Provided
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