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

• Status: Recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborator: Noordwest Ziekenhuisgroep
• Treatments: Carboplatin; Paclitaxel

Criteria

Inclusion Criteria:

• Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction.

• Surgical resectable (and/or CT scan of neck, thorax and abdomen. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled.

• T1N+ tumors are eligible.

• Tumor length longitudinal ≤ 10 cm; if larger than 10 cm, inclusion should be discussed with the principal investigator.

• If the tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction.

• Age ≥ 18.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate hematological, renal and hepatic functions defined as:

• neutrophiles ≥ 1.5 x 109/L

• platelets ≥ 100 x 109/L

• hemoglobin ≥ 5.6 mmol

• total bilirubin ≤ 1.5 x upper normal limit

• creatinine clearance (Cockroft) > 60 ml/min

• Written, voluntary informed consent

• Patients must be accessible to follow up and management in the treatment center

Exclusion Criteria:

• Past (within 5 years) or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer, not including superficial and adequately treated skin and cervical malignancies.

• Previous chemotherapy, radiotherapy and/or treatment with Interleukin-6 (IL6) receptor blockers for esophageal cancer

• Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor.

• Previous chemotherapy and/or treatment with targeted agents and/or IL6 receptor blockers for other forms of cancer within the last six months.

• Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula.

• T1N0 tumors or in situ carcinoma.

• Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation.

• Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.

• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) precluding major surgery.

• Pulmonary fibrosis and/or severely impaired lung function precluding major surgery.

• Serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine.

• Dementia or altered mental status that would prohibit the understanding and giving of informed consent

• Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding.

• Requires systemic treatment with IL6 receptor blockers or IL-6 antagonists, Tumor Necrosis Factor (TNF)-alpha blockers or other biologicals within the last six months before the first dose of trial treatment.

• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

• Has an active infection requiring systemic therapy which has not resolved 3 days (simple infection such as cystitis) to 7 days (severe infection such as pyelonephritis) prior to the first dose of trial treatment.

• Has a total cholesterol > 6.5 mmol/L despite adequate treatment with lipid-lowering agents.

• Has evidence of (latent) tuberculosis infection in patient history.

• Receiving a live or live weakened vaccine during treatment with tocilizumab

• Has evidence of acute or chronic infection with hepatitis B

• Patients with prior allogeneic stem cell or solid organ transplantation.

• Pre-existing motor or sensory neurotoxicity greater than World Health Organization (WHO) grade 1.

• Known allergy for tocilizumab or one of its excipients (sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dehydrate)