Mismatch repair deficient and proficient metestatic colorectal carcinoma and mismatch repair deficient metastatic endometrial carcinoma
Conditions
Interventions
Trade Name: Translarna
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: ATALUREN
CAS Number: 775304-57-9
Concentra
Sponsors
Amsterdam University Medical Centers location AMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Metastatic or irresectable locally advanced mismatch repair proficient or deficient colorectal carcinoma or mismatch repair deficient endometrial carcinoma - Have received or refused at least one chemotherapy treatment for metastatic disease - Life expectancy greater than 3 months - Normal organ and marrow function (as defined in protocol) - Be willing and able to provide metastasis tissue pre and post treatment by core or excissional biopsy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - (Partner is) currently pregnant or breastfeeding or is planning to become pregnant or nurture a child during the duration of the trial and a designated period thereafter. - Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti OX-40, anti-CD40 or anti-CTLA-4. - Active central nervous system metastsasis or carcinomateus meningitis - (History of) auto-immune disease - Immunodeficiency or use of immunosuppressing drugs. - Active infection - Uncontrolled intercurrent disease (for example hearth failure) - (History of) active Tuberculosis - HIV, Hep A, Hep B.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess safety and characterize toxicities of pembrolizumab combined with ataluren in patients with pMMR mCRC, dMMR mCRC and dMMR mEC. 2. To determine the immune-related progression free survival (irPFS) rate at 21 weeks and objective response rate (irORR) at 30 weeks in patients with pMMR mCRC, dMMR mCRC and dMMR mEC treated with pembrolizumab combined with ataluren using immune related response criteria (irRC). ; Secondary Objective: Overall survival (OS) at the end of study Response rate (RR) at the end of the study Immune related progression free survival (irPFS) after 30 weeks Progression free survival (PFS) after 30 weeks Comparison with MK-3475-016 study Exploratory objectives (biomarkers, T-cel activity, Neo-epitope validation, DNA sequencing differences, RNA level differences) ; Primary end point(s): Phase I: - Safety - Maximum tolerated dose (MTD) Phase II: - Immune related progression free survival (irPFS) - Objective Response rate (irORR) ; Timepoint(s) of evaluation of this end point: Phase I: - Toxicity for individual patient is monitored until day 28 followed by dose escalation or reduction in next cohort. - After 6-12 patients MTD is set. (see phase I flow chart in protocol) Phase II: - irPFS at 21 weeks - irORR at 30 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS) Response rate (RR) Immune related progression free survival (irPFS) Progression free survival (PFS) Comparison with MK-3475-016 study Exploratory research (biomakers, T-cel activation, DNA/RNA seq, Neo-epitope validation) ; Timepoint(s) of evaluation of this end point: OS, RR and comparison at end of study irPFS and PFS after 30 weeks Exploratory research during and after study | — |
Countries
Netherlands
Contacts
Public ContactAdriaan D. Bins
Amsterdam University Medical Centers location AMC
Outcome results
None listed