TGF‐β And PDL‐1 inhibition with Bintrafusp alfa in Esophageal Squamous Cell carcinoma combined with chemoradiation TheRapY (TAPESTRY)

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], Diseases [C] - Digestive System Diseases [C06]

Trial duration

24 Jun 2024 → ongoing

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-503312-32-00

EudraCT number

2020-002079-36

ClinicalTrials.gov

NCT04595149

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of the study is to assess the feasibility of bintrafusp alfa combined with definitive chemoradiation (carboplatin, paclitaxel and radiation) in terms of completion of treatment with bintrafusp alfa of patients with squamous cell carcinoma of the esophagus or gastroesophageal junction.

Secondary objectives 9

1. Incidence and severity of toxicity defined according to CTCAE v5 and Radiation Oncology Group (RTOG) criteria
2. Safety of bintrafusp alfa in combination with definitive chemoradiotherapy
3. Percentage completion of chemotherapy and radiation treatment
4. Percentage withdrawal rate from chemoradiation due to bintrafusp alfa related complications
5. Infield locoregional progression free survival
6. Any progression free survival
7. Overall survival
8. Quality of life, with a special focus on dysphagia
9. To perform exploratory biomarker analyses from tumor tissue and blood-derived samples and correlate with safety and clinical outcome

Conditions and MedDRA coding

Esophageal squamous cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically proven squamous cell carcinoma of the esophagus or gastro esophageal junction
2. Written, voluntary informed consent
3. Patients must be accessible to management and follow-up in the treatment center
4. 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
5. Locoregional recurrences without distant metastasis after surgery alone or endoscopical resection
6. 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
7. 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
8. Age ≥ 18
9. ECOG performance status 0-2
10. Adequate hematological, renal and hepatic functions
11. Tumors that cannot be passed with an endoscope for endoscopic ultrasound are eligible if all other criteria are fulfilled.

Exclusion criteria 25

1. Past or current history of malignancy other than entry diagnosis interfering with prognosis of esophageal cancer
2. 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
3. Patient with aortal involvement with high risk of bleeding or developing a fistula
4. Patients with pathological lymph nodes at both supraclavicular and truncus coeliacus level
5. Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation
6. 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
7. Previous chemotherapy, radiation and/or treatment with checkpoint inhibitors for the currently present esophageal tumor
8. Previous chemotherapy and/or treatment with targeted agents and/or checkpoint inhibitors for other forms of cancer within the last six months
9. Previous radiation to the mediastinum precluding full dose radiation of the currently present esophageal tumor
10. Presence of an esophageal stent
11. History of bleeding diathesis or major bleeding event (grade ≥ 2) in the month prior to first dose of trial treatment
12. Current use of direct oral anticoagulants or coumarins
13. Clinically significant cardiovascular disease precluding safe treatment with chemoradiation
14. 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
15. 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
16. Mental status that would prohibit the understanding and giving of informed consent
17. Inadequate caloric- and/or fluid intake despite consultation of a dietician and/or tube feeding
18. 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
19. 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
20. Active HBV/HCV. Participants on a stable dose of antiviral therapy with HBV/HCV viral load below the limit of quantification are eligible
21. 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 of trial treatment
22. Evidence of interstitial lung disease or active, non-infectious pneumonitis
23. 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
24. Administration of a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted
25. Patients with prior allogeneic stem cell or solid organ transplantation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is feasibility defined as percentage of patients that complets at least two of the three planned cylces of bintrafusp alfa

Secondary endpoints 10

1. Incidence and severity of toxicity defined according to CTCAE v5 and Radiation Oncology Group (RTOG) criteria
2. Safety of bintrafusp alfa in combination with definitive chemoradiotherapy
3. Percentage completion of chemotherapy and radiation treatment
4. Infield locoregional progression free survival
5. Any progression free survival
6. Overall survival
7. Quality of life, with a special focus on dysphagia
8. Potential biomarker development based on assessment of tumour and duodenal biopsies, faeces and blood samples
9. Occurrence of TEAEs and treatment related AEs, including abnormalities (grade ≥3) in laboratory tests
10. Patient reported outcomes other than quality of life, including but not limited to anxiety and depression, worry of cancer progression and work productivity.

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

P. O. Box 7057

City

Amsterdam

Postcode

1007 MB

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Hanneke W.M. van Laarhoven, MD, PhD

Public contact point

Organisation

Amsterdam UMC

Contact name

Hanneke W.M. van Laarhoven, MD, PhD

Third parties 1

Locations

1 EU/EEA country · 15 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