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

NCT04481256 | Recruiting DMC

• 1 other identifier: 73750
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Squamous Cell; Oesophageal Cancer

Keywords

Definitive chemoradiation; TGF-beta inhibition; PDL-1 ihibition; feasability

Outcome Measures

Primary Outcomes (1)

• Feasibility difined as the percentage of patients completing at least two cycles of bintrafusp alfa

  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.

  36 months

Secondary Outcomes (8)

• Incidence and severity of toxicity

  36 months

• Percentage completion

  36 months

• Percentage withdrawal rate

  36 months

• locoregional progression

  36 months

• progression

  36 months

Other Outcomes (1)

• Biomarker

  54 months

Study Arms (1)

1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

EXPERIMENTAL

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; Drug: Bintrafusp alfa; Drug: Paclitaxel; Drug: Carboplatin

Interventions

External beam radiotherapy RADIATION

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

1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

Bintrafusp alfa DRUG

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

Also known as: M7824

1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

Paclitaxel DRUG

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

Also known as: Taxol

1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

Carboplatin DRUG

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

1 Bintrafusp alfa, Paclitaxal, Carboplatin, Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• UMC Utrecht: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Institute Verbeeten: collaborator
• Elisabeth-TweeSteden Ziekenhuis: collaborator
• Leiden University Medical Center: collaborator
• Radiotherapeutic Institute Friesland: collaborator
• Frisius Medisch Centrum: collaborator
• Radiotherapy Group Deventer: collaborator
• Deventer Ziekenhuis: collaborator
• Rijnstate Hospital: collaborator
• Erasmus Medical Center: collaborator
• The Netherlands Cancer Institute: collaborator
• Isala: collaborator
• University Medical Center Groningen: collaborator
• Ziekenhuisgroep Twente: collaborator

Study Sites (1)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

RECRUITING

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Esophageal Neoplasms

Interventions

bintrafusp alfa protein, human; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Hanneke WM van Laarhoven, MD,PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linde M Veen, MD

CONTACT

+31 20 4443312; l.veen1@amsterdamumc.nl

Hanneke WM van Laarhoven, MD, PhD

CONTACT

+31 20 5665955; h.vanlaarhoven@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: 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 Record Dates

• First Submitted: May 26, 2020
• First Posted: July 22, 2020
• Study Start: November 11, 2020
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2030
• Last Updated: July 26, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)