TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY (TAPESTRY)

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ClinicalTrials.gov Identifier: NCT04481256

Recruitment Status : Recruiting

First Posted : July 22, 2020

Last Update Posted : January 20, 2021

See Contacts and Locations

Sponsor:

Collaborators:

UMC Utrecht

Catharina Ziekenhuis Eindhoven

Verbeeten Insituut Tilburg

Elisabeth-TweeSteden Ziekenhuis

Leiden University Medical Center

Radiotherapeutic Institute Friesland

Medisch Centrum Leeuwarden

Radiotherapy Group Deventer

Deventer Ziekenhuis

Rijnstate Hospital

Erasmus Medical Center

The Netherlands Cancer Institute

Maastro Clinic, The Netherlands

Zuyderland Medisch Centrum

Isala

University Medical Center Groningen

ZGT

Information provided by (Responsible Party):

H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Carcinoma, Squamous Cell Oesophageal Cancer	Radiation: External beam radiotherapy Drug: Bintrafusp alfa Drug: Paclitaxel Drug: Carboplatin	Not Applicable

Detailed Description:

Non-randomized feasibility study with paclitaxel, carboplatin, bintrafusp alfa, and radiation. Paclitaxel 50 mg/m2 and carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36. Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg. External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	49 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Intervention Model Description:	Non-randomized feasibility study with paclitaxel, carboplatin, bintrafusp alfa, and radiation. Paclitaxel 50 mg/m2 and carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36. Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg. External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy.
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY
Actual Study Start Date :	November 11, 2020
Estimated Primary Completion Date :	June 1, 2023
Estimated Study Completion Date :	June 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Camurati-Engelmann disease

Drug Information available for: Carboplatin

Genetic and Rare Diseases Information Center resources: Esophageal Cancer Camurati-Engelmann Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy Non-randomized feasibility study with paclitaxel, carboplatin, bintrafusp alfa, and radiation. Paclitaxel 50 mg/m2 and carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36. Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg. External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy	Radiation: External beam radiotherapy External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy Drug: Bintrafusp alfa Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg. Drug: Paclitaxel Paclitaxel 50 mg/m2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36. Drug: Carboplatin Carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36.

Arm

Intervention/treatment

Experimental: 1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy

Radiation: External beam radiotherapy

External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy

Drug: Bintrafusp alfa

Bintrafusp alfa will be given i.v. every three weeks on day 1, 22, and 43 at a dose of 2400 mg.

Drug: Paclitaxel

Paclitaxel 50 mg/m2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36.

Drug: Carboplatin

Carboplatin AUC = 2 will be given intravenously (i.v.) on days 1, 8, 15, 22, 29 and 36.

Outcome Measures

Primary Outcome Measures :

Feasibility difined as the percentage of patients completing at least two cycles of bintrafusp alfa [ Time Frame: 36 months ]
The primary outcome of this study is the percentage of patients that completes at least two cycles of bintrafusp alfa together with their chemoradiotherapy regimen.

Secondary Outcome Measures :

Incidence and severity of toxicity [ Time Frame: 36 months ]
Incidence and severity of toxicity defined according to CTCAE v5 and and Radiation Oncology Group (RTOG) criteria.
Percentage completion [ Time Frame: 36 months ]
Percentage completion of chemotherapy and radiation treatment
Percentage withdrawal rate [ Time Frame: 36 months ]
Percentage withdrawal rate from chemoradiation due to bintrafusp alfa related complications
locoregional progression [ Time Frame: 36 months ]
Infield locoregional progression free survival
progression [ Time Frame: 36 months ]
Any progression free survival
Survival [ Time Frame: 36 months ]
Overall survival
Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30)) [ Time Frame: 36 months ]
Overall Quality of life ranging from 0-100 with 100 being best Quality of Life with special focus on dysphagia
adverse events [ Time Frame: 36 months ]
To determine the number and grade of adverse events of bintrafusp alfa combined with chemoradiotherapy according to NCI common toxicity criteria (CTC) version 5

Other Outcome Measures:

Biomarker [ Time Frame: 54 months ]
To perform exploratory biomarker analyses for treatment response

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 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 (cf. Appendix A).
Adequate hematological, renal and hepatic functions defined as:
- Neutrophils ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 5.6 mmol
- Total bilirubin ≤ 1.5 x upper normal limit
- ASAT and ALAT ≤ 1.5 x upper normal limit, Alkaline Phosphatase ≤ 2.5 x upper normal limit.
- PT (INR) ≤ 1.5 x upper normal limit and aPTT ≤ 1.5 x upper normal limit.
- Creatinine clearance (Cockroft) > 60 ml/min
Written, voluntary informed consent
Patients must be accessible to management and follow-up in the treatment center

Exclusion Criteria:

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.
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.
Persisting grade >1 NCI CTCAE 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, grade ≤2 sensory neuropathy is acceptable.
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.
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.
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.
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.
Evidence of interstitial lung disease or active, non-infectious pneumonitis.
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.
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.
Patients with prior allogeneic stem cell or solid organ transplantation.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04481256

Contacts

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Contact: Linde Veen	020-5665955	l.veen1@amsterdamumc.nl
Contact: Hanneke WM van Laarhoven, MD, PhD	020-5665955	h.vanlaarhoven@amsterdamumc.nl

Locations

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Netherlands
Academic Medical Center, Medical Oncology	Recruiting
Amsterdam, Netherlands, 1100 DD
Contact: H WM van Laarhoven, MD, PhD, PhD 31 20 5665955 h.vanlaarhoven@amc.uva.nl
Contact: Lyda ter Hofstede 31 20 5668229 trialmedonc@amc.uva.nl
Principal Investigator: H. WM van Laarhoven, MD, PhD, PhD

Sponsors and Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)