Clinical Trial: Combination of MK3475 and Metronomic Cyclophosphamide in Patients With Advanced Sarcomas : Multicentre Phase II Trial

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Combination of MK3475 and Metronomic Cyclophosphamide in Patients With

Brief Summary: This is a multicenter study assessing efficacy of the MK 3475 (Pembrolizumab) in combination with metronomic cyclophosphamide in patients with advanced sarcomas.

Detailed Summary:

This is a phase 2 trial with 5 strata :

  • Leiomyosarcoma : 33 patients
  • Undifferentiated sarcoma : 33 patients
  • Sarcomas others : 33 patients
  • Osteosarcoma : 33 patients
  • GIST : 31 patients

Sponsor: Institut Bergonié

Current Primary Outcome: Assessment of the efficacy of MK3476 associated with Metronomic Cyclophosphamide per RECIST v1.1 criteria [ Time Frame: 6 months ]

This primary objective of this study is to assess the efficacy of MK3475 and Metronomic

Cyclophosphamide (CP) independently for 5 strata as per RECIST v1.1 criteria :

In terms of 6-month objective response and 6-months non progression for:

  • Advanced leiomyosarcoma
  • Advanced undifferentiated sarcoma
  • Advanced other sarcoma
  • Advanced osteosarcoma

In terms of·6-month non progression for:

Advanced GIST



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Efficacy of MK3475 and Metronomic CP in terms of Best overall response [ Time Frame: participants will be followed for the duration of treatment, an expected average of 6-months ]
    Assessment of the efficacy of MK3475 and Metronomic CP in terms of best overall response (as per RECIST v1.1 criteria)
  • Efficacy of MK3475 and Metronomic CP in terms of Progression-free Survival [ Time Frame: Progression-free survival assessed at 12 months ]
    Assessment of the efficacy of MK3475 and Metronomic CP in terms of 1-year progression-free survival (as per RECIST v1.1 criteria)
  • Efficacy of MK3475 and Metronomic CP in terms of Immune_related Response [ Time Frame: Immune-related response assessed at 6 months ]
    Assessment of the efficacy of MK3475 and Metronomic CP in terms of 6-months immune-related response (as per Wolchok 2009)
  • Efficacy of MK3475 and Metronomic CP in terms of Overall Survival. [ Time Frame: Overall survival assessed at 12 months ]
    Assessment of the efficacy of MK3475 and Metronomic CP in terms of 1-year overall survival
  • Exploration of blood cytokines levels (TNFγ, TNFα, TGFβ, IL2, 4, 6, 10) (ELISA) [ Time Frame: Blood samples collected at different time points : Baseline, Day 8 cycle 1, Day 8 cycle 2, Day 8 cycle 3, Day 8 cycle 4, Day 8 Cycle 6 and at progression ]
  • Exploration of blood VEGF, Svegfr2 and TPS-1 levels (ELISA) [ Time Frame: Blood samples collected at different time points : Baseline, Day 8 cycle 1, Day 8 cycle 2, Day 8 cycle 3, Day 8 cycle 4, Day 8 Cycle 6 and at progression ]
  • Exploration of lymphocytes subpopulations monitoring, CD8+/Treg ratio (flow cytometry) [ Time Frame: Blood samples collected at different time points : Baseline, Day 8 cycle 1, Day 8 cycle 2, Day 8 cycle 3, Day 8 cycle 4, Day 8 Cycle 6 and at progression ]
  • Exploration of Plasma levels of Kynurenine and Kynurenine to Tryptophan ratio (ELISA and LC/MS) [ Time Frame: Blood samples collected at different time points : Baseline, Day 8 cycle 1, Day 8 cycle 2, Day 8 cycle 3, Day 8 cycle 4, Day 8 Cycle 6 and at progression ]


Original Secondary Outcome: Same as current

Information By: Institut Bergonié

Dates:
Date Received: March 12, 2015
Date Started: March 2015
Date Completion: March 2018
Last Updated: November 8, 2016
Last Verified: November 2016