Blood-borne Assessment of Stromal Activation in Esophageal Adenocarcinoma to Guide Tocilizumab Therapy

Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study ID
NCT04554771
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Esophageal Adenocarcinoma
  • Oesophageal Adenocarcinoma
  • Resectable Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tocilizumab 20 Mg/mL Intravenous Solution — DRUG
    tocilizumab 8 mg/kg with a maximum of 800 mg intravenously on day 1, 15 and 29 of standard of care neoadjuvant chemoradiation
  • Paclitaxel — DRUG
    Paclitaxel 50 mg/m2 will be given intravenously on days 1, 8, 15, 22 and 29
  • Carboplatin — DRUG
    Carboplatin AUC = 2 will be given intravenously on days 1, 8, 15, 22 and 29
  • External beam radiotherapy — RADIATION
    External beam radiotherapy will be delivered to a total dose of 41.4 Gy in 23 fractions of 1.8 Gy, 5 fractions per week starting the first day of the first cycle of chemotherapy

Study Details

The primary objective of this study is to demonstrate that stroma-targeting by tocilizumab in patients with adenocarcinoma of the esophagus or gastroesophageal junction with highly activated stroma increases efficacy of chemoradiotherapy measured by pathological response according to the Mandard criteria. Patients will be grouped for ADAM12, a non-invasive blood-borne marker of stromal activation.

Key Dates

Start date
Jan 27, 2021
Status verified
Jul 2024
Primary completion
Oct 10, 2022
Completion
Apr 10, 2028

Study Design

Enrollment
41 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: ADAM12 high with tocilizumab and standard of care
    Patients have serum ADAM12 higher than 203ng/mL. Patients will receive tocilizumab 8 mg/kg with a maximum of 800 mg intravenously on day 1, 15 and 29 in addition to paclitaxel 50mg/m2 and carboplatin AUC 2 intravenously on day 1, 8, 15, 22 and 29. External beam radiation of 41.4 Gy will be given in 23 fractions. Surgery will be planned approximately in week 13-15, which is 8 to 10 weeks after the end of chemoradiation.
  • Active Comparator: ADAM12 high with standard of care
    Patients have serum ADAM12 higher than 203ng/mL. Patients will receive paclitaxel 50mg/m2 and carboplatin AUC 2 intravenously on day 1, 8, 15, 22 and 29. External beam radiation of 41.4 Gy will be given in 23 fractions. Surgery will be planned approximately in week 13-15, which is 8 to 10 weeks after the end of chemoradiation.
  • Experimental: ADAM12 low with tocilizumab and standard of care
    Patients have serum ADAM12 lower than 203ng/mL. Patients will receive tocilizumab 8 mg/kg with a maximum of 800 mg intravenously on day 1, 15 and 29 in addition to paclitaxel 50mg/m2 and carboplatin AUC 2 intravenously on day 1, 8, 15, 22 and 29. External beam radiation of 41.4 Gy will be given in 23 fractions. Surgery will be planned approximately in week 13-15, which is 8 to 10 weeks after the end of chemoradiation.
  • Active Comparator: ADAM12 low with standard of care
    Patients have serum ADAM12 lower than 203ng/mL. Patients will receive paclitaxel 50mg/m2 and carboplatin AUC 2 intravenously on day 1, 8, 15, 22 and 29. External beam radiation of 41.4 Gy will be given in 23 fractions. Surgery will be planned approximately in week 13-15, which is 8 to 10 weeks after the end of chemoradiation.

Primary Outcome Measure

Efficacy defined as pathological response to chemoradiotherapy according to the Mandard criteria [ Time Frame: 34 months ]

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