Study of pembrolizumab combined with ataluren in Patients with metastatic pMMR and dMMR colorectal cancer adenocarcinomas or metastatic dMMR endometrial carcinoma: the ATAPEMBRO study.
- Conditions
- advanced cancer of the colonmetastastic colon cancer10027476
- Registration Number
- NL-OMON55845
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 47
- Metastatic or irresectable locally advanced mismatch repair proficient or
deficient colorectal carcinoma or mismatch repair deficient endometrial
carcinoma or mismatch repair deficient stomach carcinoma or mismatch repair
deficient small bowel carcinoma 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.
- (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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The endpoints are similar to the endpoints in the MK-3475-016 trial, with minor<br /><br>adaptations to accommodate the new Q3W treatment regimen. Also, for ethical<br /><br>reasons dMMR patients can be included after 1 metastatic treatment line<br /><br>(instead of 2 metastatic or non-metastatic chemotherapy lines required in the<br /><br>MK-3475-016 trial). Taking the caveats of cross-trial comparisons into account,<br /><br>the close analogy to the MK-3475-016 study facilitates case-matched cross-trial<br /><br>comparisons of the results of both studies. This way, we will be able to<br /><br>estimate whether further exploration of this combination is warranted.</p><br>
- Secondary Outcome Measures
Name Time Method <p>To determine the overall survival of patients with pMMR CRC, dMMR mCRC, dMMR<br /><br>EC, , dMMR SBC, dMMR SC treated with pembrolizumab combined with ataluren.<br /><br>To estimate irPFS and PFS in patients with pMMR CRC, dMMR mCRC, dMMR EC, dMMR<br /><br>SBC, dMMR SC treated with pembrolizumab combined with ataluren at 30 weeks<br /><br>using irRC and RECIST<br /><br>To estimate best overall response rate and disease control rate in patients<br /><br>with pMMR CRC, dMMR mCRC and dMMR EC treated with pembrolizumab combined with<br /><br>ataluren.<br /><br>To assess safety and characterize toxicities of pembrolizumab combined with<br /><br>ataluren in patients with pMMR CRC, dMMR mCRC and dMMR EC.<br /><br>To compare the outcomes of abovementioned primary and secondary study<br /><br>objectives with a series of case-matched controls treated within the<br /><br>MK-3475-016 study.</p><br>