Tapestry: Addition of TGF-β and PDL-1 Inhibition to Definitive Chemoradiation in Esophageal Squamous Cell Carcinoma (TAPESTRY)
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|ClinicalTrials.gov Identifier: NCT04595149|
Recruitment Status : Recruiting
First Posted : October 20, 2020
Last Update Posted : January 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Neoplasm, Esophagus Malignant Esophagus Tumor Neoplasm, Esophageal||Combination Product: Bintrafusp alfa||Phase 2|
This is a non-randomized feasibility study in which patients with esophageal squamous cell carcinoma receive bintrafusp alfa (B), combined with paclitaxel (P), carboplatin (C), and radiation (RT). For safety reasons the first ten patients will be treated in a maximum of four selected hospitals. If no unexpected safety signals occur, the study will start in all participating centers.
Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22, 29, and 36. 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 (see below for details on radiation technique).
Bintrafusp alfa will be given iv every three weeks on day 1, 22, and 43 at a dose of 2400 mg.
Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6 Wk 7 Day 1 Day 8 Day 15 Day 22 Day 29 Day 36 Day 43 __________________________________________________
P P P P P P C C C C C C B B B RTx5 RTx5 RTx5 RTx5 RTx5 RTx3
__________________________________________________ P = paclitaxel; C = carboplatin, B = bintrafusp alfa RT = radiotherapy
Feasibility of this treatment strategy is the main focus of this study. In this study feasibility is defined as ≥80% of patients completing two cycles (of in total three) cycles of bintrafusp alpha. In the ART-DECO study, which included a similar patient population, more than 80% of patients was able to receive five cycles of carboplatin and paclitaxel (i.e. up to week 5) (personal communication dr. Hulshof). Therefore, the investigators will regard treatment with Bintrafusp alfa during chemoradiation feasible if ≥80% of patients complete two cycles of bintrafusp alfa, while with a completion rate ≤62% the treatment will be regarded unfeasible.
The primary end point of this feasibility study is the percentage of patients completing bintrafusp alfa treatment. This study requires 41 subjects to decide whether the proportion completing at least two cycles of bintrafusp alfa, P, is less than or equal to 0.62 or greater than or equal to 0.80. If the number of patients completing two or more cycles of Bintrafusp alfa is 31 or more, the hypothesis that P ≤ 0.62 is rejected with a target error rate of 0.05 and an actual error rate of 0.048. If the number of patients completing two or more cycles of bintrafusp alfa is 30 or less, the hypothesis that P ≥ 0,80 is rejected with a target error rate of 0.20 and an actual error rate of 0.182. The test statistic used is the one-sided one-sample test for binomial proportion, testing against the fixed reference proportion of 0.62. Taking into account 20% drop-out, 52 patients need to be included in the study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY|
|Actual Study Start Date :||November 30, 2020|
|Estimated Primary Completion Date :||November 1, 2023|
|Estimated Study Completion Date :||November 1, 2028|
Adding bintrafusp alfa (a combined TGF-β en PDL-1 inhibitor) to definitive chemoradiation with Paclitaxel and Carboplatin
Combination Product: Bintrafusp alfa
Bintrafusp alfa (M7824, MSB0011359C) is an innovative first-in-class, bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGFβRII or TGFβ Trap) covalently linked via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin G1 (IgG1) antibody blocking programmed death ligand 1 (anti-PD-L1). Bintrafusp alfa is the international nonproprietary name for M7824.
Other Name: M7824
- Feasibility bintrafusp alfa [ Time Frame: 36 months ]The primary endpoint is feasibility defined as percentage completion of treatment with bintrafusp alfa.
- Toxicity according to different criteria [ Time Frame: 36 months ]• Incidence and severity of toxicity defined according to CTCAE v5 and Radiation Oncology Group (RTOG) criteria.
- Completion of treatment [ Time Frame: 36 months ]Percentage completion of chemotherapy and radiation treatment
- Progression free survival [ Time Frame: 36 months ]Any progression free survival
- Survival [ Time Frame: 36 months ]Overall survival
- QOL [ Time Frame: 36 months ]Quality of life, with a special focus on dysphagia
- Local progression free survival [ Time Frame: 36 months ]Local in-field progression free survival
- Biomarker development [ Time Frame: 36 months ]Potential biomarker development based on assessment of tumour and duodenal biopsies, blood samples and faecal samples
- Patient reported outcomes [ Time Frame: 36 months ]Patient reported outcomes other than quality of life, including but not limited to anxiety and depression, worry of cancer progression and work productivity.
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): NCT04595149
|Contact: Hanneke WM van Laarhoven, M.D, PhD||31 20 firstname.lastname@example.org|
|Contact: Linde Veen||31 20 email@example.com|
|Amsterdam, Noord-Holland, Netherlands, 1081HV|
|Contact: Linde Veen +31612538338 firstname.lastname@example.org|
|Principal Investigator:||Hanneke WM van Laarhoven, M.D., PhD||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|