Anti-PD-1, Capecitabine, and Oxaliplatin for the first-line treatment of dMMR esophagogastric cancer (AuspiCiOus-dMMR): a proof-of-principle study

Phase 2

Recruiting

Conditions: cancer of esophagus and stomach
Metastatic upper gastrointestinal cancer
10017991

Registration Number: NL-OMON52108

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

- Male or female adult patients (> 18 years)
- Primaire tumor or metastasis accessible for repeat fresh histological biopsies
- dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2, and MSH6
- Patients with histologically confirmed diagnosis of metastatic or
irresectable HER2 negative adenocarcinoma of the stomach or oesophagus;
patients with HER2 positive disease are eligble when treatment with trastuzumab
is contraindicated. If histology cannot be obtained, cytology is acceptable to
prove metastatic disease
- Patients with metastatic or irresectable adenocarcinoma of the stomach or
oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable
or metastatic disease. Palliative radiotherapy on the primary tumor or a
metastatic lesion is allowed if other untreated lesions eligble for evaluation
are present
- Measurable disease as assessed by RECIST 1.1
- ECOG (WHO) performace status 0-2
- Patient has adequate hepatic, renal and hematological function

Exclusion Criteria

- Severe renal impairment (CLcr <= 30 ml/min)
- Any prior anti-cancer chemotherapy, biologic or investigational therapy for
metastatic or irresectable stomach or oesophageal cancer
- Disease progression within six months after completion of (neo)adjuvant
chemotherapy containing a fluoropyrimidine and/or platinum compound. (Disease
progression within 6 months after completion of neoadjuvant chemoradiation
carboplatin AUC 2 and paclitaxel 50 mg/m2 is allowed.)
- Patient has known brain metastases, unless previously treated and
well-controlled for at least 3 months (defined as clinically stable, no edema,
no steroids and stable in 2 scans at least 4 weeks apart).
- Past or current malignancy other than entry diagnosis interfering with
prognosis of metastatic esophagogastric cancer.
- Complete dihydropyrimidine dehydrogenase deficiency.
- Use of other investigational drugs within 30 days of enrollment.
- Patient is enrolled in any other clinical protocol or investigational trial
that will interfere with the primary endpoint of the current study.
- Treatment within 4 weeks with DPD inhibitors, including sorivudine or its
chemically related analogues such as brivudine.
- Pre-existing motor or sensory neurotoxicity greater than CTCAE grade 1.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess changes in Interferon gamma (IFN-*) expression signature and<br /><br>infiltration of cytotoxic T cells in the tumor immune microenvironment at<br /><br>baseline, after two courses of CapOx and after 6 weeks of PD-1 inhibition<br /><br>maintenance using the anti PD-1 monoclonal antibody retifanlimab in dMMR<br /><br>patients.</p><br>

Secondary Outcome Measures