TGF-β And PDL-1 inhibition with Bintrafusp alfa in Esophageal Squamous Cell carcinoma combined with chemoradiation TheRapY (TAPESTRY)
- Conditions
- esophageal squamous cell carcinomaesophagus cancer1001799010017991
- Registration Number
- NL-OMON52872
- Lead Sponsor
- Medische oncologie
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 67
- Histologically proven squamous cell carcinoma of the esophagus or gastro
esophageal junction.
- Surgically irresectable (T1-T4a, N0 or N+, M0), as determined by Endoscopic
Ultra Sound (EUS), PET scan and diagnostic CT scan of neck, thorax and abdomen.
Patients with M1 disease solely on the basis of supraclavicular metastasis are
eligible. Patients with resectable tumors refusing radical surgery or
inoperable patients due to comorbidity are eligible.
- Locoregional recurrences without distant metastasis after surgery alone or
endoscopical resection
- Locoregional recurrences without distant metastasis after neoadjuvant
chemoradiation + resection or definitive chemoradiation outside the previously
irradiated area, provided that full dose of radiation can safely be delivered.
- Tumors that cannot be passed with an endoscope for endoscopic ultrasound are
eligible if all other criteria are fulfilled.
- 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.
- ECOG performance status 0-2
- Adequate hematological, renal and hepatic functions.
- Written, voluntary informed consent
- Patients must be accessible to management and follow-up in the treatment
center
- Past or current history of malignancy other than entry diagnosis interfering
with prognosis of esophageal cancer.
- Patient with tracheo-esophageal fistula or extension into the mucosal layer
of the trachea, highly at risk to develop fistula. Thus, tumor extension to the
trachea is allowed, but not through the trachea.
- Patient with aortal involvement with high risk of bleeding or developing a
fistula.
- Patients with pathological lymph nodes at both supraclavicular and truncus
coeliacus level.
- Pregnancy (positive serum pregnancy test), planning to become pregnant, and
lactation.
- Patient (male or female) in the reproductive age 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.
- Previous chemotherapy, radiation and/or treatment with checkpoint inhibitors
for the currently present esophageal tumor.
- Previous chemotherapy and/or treatment with targeted agents and/or checkpoint
inhibitors for other forms of cancer within the last six months.
- Previous radiation to the mediastinum precluding full dose radiation of the
currently present esophageal tumor.
- Presence of an esophageal stent.
- History of bleeding diathesis or major bleeding event (grade >= 2) in the
month prior to first dose of trial treatment.
- Current use of direct oral anticoagulants or coumarins.
- Clinically significant cardiovascular disease precluding safe treatment with
chemoradiation.
- Evidence of pulmonary fibrosis and/or clinically significant impairment of
lung function precluding safe treatment with chemoradiation. In case of doubt
about pulmonary function, a lung function test should be performed and, in case
of abnormalities, discussed with the principle investigator.
- 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.
- 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.
- Has an active autoimmune disease that has required systemic treatment in past
2 years (i.e. with use of disease modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (e.g., thyroxine for patients
with a history of autoimmune-related hypothyroidism, insulin for patients with
type 1 diabetes mellitus, or physiologic corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment. Patients with vitiligo with dermatological manifestations only are
eligible to enter the study.
- Diagnosis of HIV unless stable on antiretroviral therapy for at least 4
weeks, no evidence of multi-drug resistance, viral load of < 400 copies/ml and
CD4+ T-cells >= 350 cells/µl.
- Active HBV/HCV. Participants on a stable dose of antiviral therapy with
HBV/HCV viral load below the limit of quantification are eligible.
- A diagnosis of immunodeficiency or is receiving systemic steroid therapy (>10
mg/day prednisone or equivalent) or any other form of immunosuppressive therapy
within 7 days prior to the first dose
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is feasibility defined as percentage of patients that<br /><br>complets at least two of the three planned cylces of bintrafusp alfa. Patients<br /><br>that do not complete treatment with bintrafusp alfa for reasons other than<br /><br>toxicity will be replaced and not included in the analysis of the primary end<br /><br>point. </p><br>
- Secondary Outcome Measures
Name Time Method