Blood-borne Assessment of Stromal activation in esophageAL adenocarcinoma to guide tocilizumab Therapy: a randomized phase II proof-of-concept study (BASALT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Jan 2021 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509458-77-00

EudraCT number

2020-002909-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective of this study is to demonstrate that stroma-targeting by tocilizumab in esophageal adenocarcinoma patients with highly activated stroma increases efficacy of chemoradiotherapy measured by pathological response according to the Mandard criteria.

Secondary objectives 1

1.  Efficacy and mechanism of action of tocilizumab with neoadjuvant chemoration against esophagogastric cancer by: o R0 resection rate o Progression free survival o Overall survival o IL6-STAT3 pathway inhibition measured by gene expression analysis o Levels of IL-6 in serum. o Phosphorylated STAT3 and stromal abundance measured by immunohistochemistry in formalin-fixed paraffin-embedded tumor tissue  Levels of ADAM12 in tumor biopsies and serum to evaluate ADAM12 as a predictive biomarker for response to treatment.  Incidence and severity of toxicity defined according to CTCAE v5.0 and Radiation Oncology Group (RTOG) criteria.  Incidence and severity of post-operative complications according to the Clavien - Dindo classification.  Percentage completion of chemotherapy and radiation treatment  Percentage withdrawal rate from surgery due to tocilizumab related complications  Percentage delay of surgery due to tocilizumab related complications

Conditions and MedDRA coding

Esophageal adenocarcinoma, esophageal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Histologically proven adenocarcinoma of the esophagus or gastroesophageal junction or high grade dysplasia with high clinical suspicion for adenocarcinoma which will be treated accordingly. - Surgical resectability ( 60 ml/min. - If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative pregnancy test (urine or serum; beta-human chorionic gonadotropin (β-hCG)) documented prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug and after the end of treatment as recommended. - Written, voluntary informed consent. - Patients must be accessible to follow up and management in the treatment center.

Exclusion criteria 1

1. - 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 IL-6 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 IL-6 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, 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 WHO grade 1. - Known allergy for tocilizumab or one of its excipients (sucrose, polysorbate 80, disodium phosphate dodecahydrate, sodium dihydrogen phosphate dehydrate).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is pathological response to chemoradiotherapy according to the Mandard criteria.

Secondary endpoints 2

1. Secondary endpoints are:  R0 resection rate.  Progression free survival  Overall survival  IL-6-STAT3 pathway inhibition based on gene expression analysis  pSTAT3 and stromal abundance in formalin-fixed paraffin-embedded tumor tissue  Levels of IL-6 in serum.  Levels of ADAM12 in tumor biopsies and serum in relation to pathological response according to the Mandard criteria.  Incidence and severity of toxicity defined according to CTCAE v5.0 and Radiation Oncology Group (RTOG) criteria.
2.  Incidence and severity of post-operative complications according to the Dindo classification.  Percentage completion of chemotherapy and radiation treatment  Percentage withdrawal rate from surgery due to tocilizumab related complications  Percentage delay of surgery due to tocilizumab related complications

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Prof. Dr. H. Van Laarhoven

Public contact point

Organisation

Amsterdam UMC

Contact name

Prof. Dr. H. Van Laarhoven

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications