Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

retrospective

Christina Muijs, Dr.

H. Rutten, MD

M. Berbee, MD, PHD

P. van Rossum, MD, PHD

H.W.M. van Laarhoven, MD, PHD

J. Nuyttens, MD, PHD

B. Wijnhoven, MD, PHD

Yvonne Klaver, MD, PHD

Christina Muijs, MD, PHD

C. T. Muijs, MD, PHD

J. A. Langendijk, Prof., MD, PHD

B. van Etten, MD, PHD

J. J. de Haan, MD, PHD

Meindert Sosef, MD

G Meijer, PHD

The aim of this project is to develop and validate NTCP-models for complications after nCRT (and surgical resection), that can be uses for model-based dose optimization for PhRT and PRT, and for model-based selection for PRT, in patients with esophageal cancer

Plan of investigation

In the present project we aim to evaluate two potential strategies to predict and consider a broad spectrum of complications for radiotherapy plan optimization and patient selection:

A comprehensive set of separate NTCP-models for several cardiopulmonary and post-operative complications after nCRT, which results in an NTCP-profile.

A single multivariable NTCP-model for a so-called Complication Sum Score (CSS), which is a single composite complication endpoint including all complications after nCRT, weighted depending on severity and impact.

These prediction models can be used for RT plan optimization and patient selection.

In order to develop these prediction models the project consortium brings together existing prospective data registries for esophageal cancer, namely the Dutch Upper GI Cancer Audit (DUCA) and the Dutch Cancer Registry (NKR) (as well as the POCOP study).

The data of these registries will be linked to a retrospective radiotherapy database using the ProTRAIT infrastructure, resulting in a dataset of over 2000 patients.

In this retrospective cohort study, we will focus on esophageal cancer patients who were treated with nCRT, and for whom an esophagectomy was intended. We will include the patients who received nCRT and the esophagectomy in one of the participating centers. Patients who only received nCRT in one of the participating centers and for whom surgical resection was omitted will be included as well. Detailed eligibility criteria can be found in that section.

Eligible patients will be identified by the Dutch Cancer Registry. The surviving patients will be asked to provide informed consent for participation in this study, permission to combine the different data registries and for future use of their data. Patients who died will be included as well, unless they objected agains the use of there data in the participating centers.

Of the participating patients, the radiotherapy plan-CT and treatment plans (i.e. RTplan, RT struct, RT dose), will be pseudo-anonymized, uploaded and transferred to the UMCG data platform, by the participating radiotherapy centers.

A third trusted party, Zorg TTP, will be responsible for the pseudonymization of the three data sources; the Dutch upper GI cancer audit (DUCA), the Dutch Cancer Registry (NKR) and the RTregistry. After that the linkage will be performed at the UMCG.

Prediction Models for Complications After CRT in Esophageal Cancer

Postoperative complications (graded by ECCG classification (3) ):

Atrial fibrillation ≥grade 2

Pneumonia ≥grade 2

Respiratory failure requiring re-intubation

Anastomotic leakage ≥ grade 2

Pericardial effusion

Myocardial infarction and other acute coronary events

Heart failure Pericardial effusion

Myocardial infarction and other acute coronary events

Heart failure

Atrial fibrillation

Complication Sum Score, that will be determined in Delphi consensus

Patient-rated fatigue / daily functioning

Hospitalization after esophagectomy (days)

Intensive care unit stay after esophagectomy (days)

Dutch Cancer Society

Comprehensive Cancer Centre The Netherlands

Dutch Institute for Clinical Auditing (DICA)

ZorgTTP

University Medical Center Groningen

Gland and Hormone Related Diseases

Stomach Neoplasms

Pancreatic Neoplasms

Stomach Cancer

Pancreatic Cancer

Participants receive BL-B01D1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.

BL-B01D1

Hai Zhu, PHD

Sa Xiao, PHD

Lin Shen, PHD

Li Chen

Meili Sun

Qing Wen

Xuelei Ma

Diansheng Zhong

Ji Zhu

In phase Ia study, the safety and tolerability of BL-B01D1 in patients with locally advanced or metastatic gastrointestinal tumor and other solid tumor will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-B01D1.

In phase Ib study, the safety and tolerability of BL-B01D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-B01D1 in patients with locally advanced or metastatic gastrointestinal tumor and other solid tumor will be evaluated.

A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumor and Other Solid Tumor

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-B01D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumor and Other Solid Tumor

DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.

MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .

The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B01D1

TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1 .

Maximum serum concentration (Cmax) of BL-B01D1 will be investigated.

Time to maximum serum concentration (Tmax) of BL-B01D1 will be investigated

Half-life (T1/2) of BL-B01D1 will be investigated

AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.

CL in the serum of BL-B01D1 per unit of time will be investigated

Ctough is defined as the lowest serum concentration of BL-B01D1 prior to the next dose will be administered

Incidence and titer of ADA of BL-B01D1 will be evaluated

Incidence and titer of Nab of BL-B01D1 will be evaluated.

ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.

The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]).

The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.

The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Prediction Models for Complications After CRT in Esophageal Cancer	NCT06366828	The Aim of This...	retrospective	18 Years - 100 Years	University Medical Center Groningen
A Study of BL-B01D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumor and Other Solid Tumor	NCT05262491	Gastrointestina...	BL-B01D1	18 Years - 75 Years	Sichuan Baili Pharmaceutical Co., Ltd.

Spots Global Cancer Trial Database for esophageal cancer (ec)