Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Liver Neoplasms

Thoracic Neoplasms

Erythema Multiforme

Respiratory Tract Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients suffering from primary malignant thoracic tumoral pathology or second line patients having had a therapy pause of at least 6 weeks.

DCE-CT of thoracic tumors as an early biomarker for treatment monitoring in comparison with morphologic criteria.

Extra DCE-CT scan

Maarten Van Hoorickx

Kenneth Coenegrachts, MD, PhD

Jolien Buyle

Veerle Surmont, Prof, Dr.

Veerle Surmont, Prof, MD

DCE-CT of thoracic tumors as an early biomarker for treatment monitoring in comparison with morphologic criteria.

1. Rationale of the clinical investigation

   For the evaluation of response to anti-tumoral therapy in thoracic tumors, merely morphologic information is often not sufficient for early response evaluation as dimensions of the oncologic lesions are not changing during the first weeks of treatment. To be able to measure functional changes, dynamic contrast-enhanced CT (DCE-CT) seems promising as a biomarker for early therapy monitoring.

   Having an early biomarker for treatment monitoring will allow to increase patients' prognosis if a non-responder is earlier detected, will optimize the use of expensive treatments, is expected to shorten hospitalization and shorten absence at work, and to decrease side-effects of (adjuvant) medication.
2. Objective of the study

2.1.Primary objectives The primary objective is to investigate the potential of functional imaging (i.e. DCE-CT), as analyzed by the Hyperfusion analytic software, as an early biomarker for the evaluation of therapy response in primary thoracic malignancy.

2.2.Secondary objectives

There are two secondary objectives:

1. To define internal system parameters and perfusion parameter thresholds that maximize the accuracy of the outcomes and to define the correct category (PD, SD, PR, CR); and
2. To compare the predicted categorization to the assessed RECIST1.1 categorization.
3. Endpoints 3.1.Primary Endpoint The primary endpoint is to directly compare the biomarker of the HF analysis software at week 3 (+- 1 week) and week 8 (+- 3 weeks) with the eventually reported Progression-Free Survival (PFS) intervals and Overall Survival (OS) in this study. PFS intervals are determined by the clinician and are based on RECIST1.1 and additional clinical and biochemical progression markers. The focus will be on evaluating the accuracy of the prediction as well as how early the prediction was correct.

3.2.Secondary Endpoints There are two secondary endpoints corresponding to the two secondary objectives.

1. The internal parameters for the HF biomarker, e.g. magnitude of the Ktrans decrease, and the change in volume of unhealthy tissue, need to be determined to define the classification (PD, SD, PR and CR) by the HF analysis software. These parameters are optimized to optimally predict the classification according to PFS and OS. This will be done by splitting the data into a train and test set to ensure generalization.
2. The classification of the HF analysis software will be compared to the purely morphological classification by RECIST1.1 to identify correlation. Furthermore, some cases will be investigated where the HF analysis performs noticeably better or worse than RECIST1.1 in predicting PFS and OS. Finally, the difference in time to the first correct prediction is compared between HF and RECIST1.1.

4.Study Design

This prospective study is part of the clinical β-phase. We aim to test pre-release versions of the Hyperfusion.ai software under real-world working conditions in a hospital (clinical) setting. It is important to note, though, that the results of the software analysis will not be used by interpreting physicians to alter clinical judgement during the course of the clinical trial.

A prospective study including 100 inoperable patients in UZ Gent suffering from primary thoracic malignancy (≥15mm diameter) will be conducted. For this study, in total 3 CT scan examinations of the thorax will be performed (a venous CT examination of the thorax in combination with a DCE-CT scan of the tumoral region).

All patients will be recruited from the pulmonology department. Oncologic patients are clinically referred with certain intervals for a clinically indicated CT scan (being part of standard care). In the study, two clinical CT examinations that are performed standard of care (baseline CT examination and CT examination at week 8 (+- 3 weeks) after start of systemic therapy) will be executed by also adding a DCE-image of the lung adenocarcinoma to this examination. This DCE-image is performed during the waiting time before the venous/morphologic phase. Consequently, from a clinical point-of-view, the time to scan remains exactly the same. With regard to the contrast agent, an identical amount is injected as is the case in standard of care, but the contrast bolus is split in two parts - see also addendum with DCE protocol.

In this study there is one additional CT-examination (DCE-scan of the thoracic malignancy in combination with venous CT scan of the thorax) at week 3 (± 1 week).

Morphologic criteria are being compared with analysis of functional (perfusion) CT imaging.

DCE-CT of Thoracic Tumors as an Early Biomarker for Treatment Monitoring in Comparison With Morphologic Criteria

The HF biomarker is calculated from DCE perfusion and permeability metrics such as arterial blood flow fraction (alpha), total blood plasma flow (F_p), volume transfer coefficient (K-trans), extracellular volume ratio reflecting vascular permeability (v_e) and plasma volume ratio (v_p). Additionally, semi-quantitative DCE signal metrics, such as signal enhancement and time until contrast agent arrival, may also be taken into account.

PFS intervals are determined by the clinician and are based on RECIST1.1 and additional clinical and biochemical progression markers. The focus will be on evaluating the accuracy of the prediction as well as how early the prediction was correct.

The classification system will be optimized to optimally predict the classification according to PFS and OS. This will be done by splitting the data into a train and test set to ensure generalization.

The difference in time to the first correct prediction is compared between HF and RECIST1.1.

University Hospital, Ghent

Hyperfusion

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bevacizumab

Antibodies

Antibodies, Monoclonal

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Bevacizumab 5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle. Temsirolimus 5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle. First tumor biopsy during screening visit and Second at the end of Cycle 1. DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1.

5 mg/kg By Vein Over 90 Minutes on Day 1 of Each 21 Day Cycle

5 mg By Vein Over 30-60 Minutes on Days 1, 8, 15 of Each 21 Day Cycle

2 teaspoons each time: 4xDay Cycle 1 after start of first infusion; at Day 8 of Cycle 1; at Day 15 of Cycle 1; and at end of Cycle 1.

Additional Blood Drawn

First tumor biopsy during screening visit and Second at the end of Cycle 1

Biopsy

DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging) scan during screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1

DCE-MRI Scan

Sarina Piha-Paul, MD

The goal of this clinical research study is to find the highest tolerable dose of Avastin (bevacizumab) and Torisel (temsirolimus) that can be given, in combination, to patients with advanced cancer that has spread or is unable to be surgically removed. The safety of this drug combination will also be studied.

The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients necessary for tumor growth.

Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of bevacizumab and temsirolimus combined, based on when you joined this study. Up to 13 dose levels of the study drug combination will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the study drug combination is found.

If you choose to enroll in the expansion group of patients being treated at the highest tolerable dose of the study drug combination found, you will be required to undergo added testing, as follows:

* You will have additional blood drawn (about 2 teaspoons each time) during Cycle 1. This blood will be drawn before you begin taking the study drugs; on Day 1 at about 1, 4, 8, and 24 hours after the start of your first infusion; at Day 8 of Cycle 1; at Day 15 of Cycle 1; and at the end of Cycle 1. The blood will be used to see how the study drug combination acts in the body and to learn its effect on cancer cells.
* You will have 2 tumor biopsies performed. These samples will be used to see how the study drug combination acts in the body and to learn its effect on cancer cells. These tumor biopsies will be performed during the screening visit and at the end of Cycle 1. To perform a tumor biopsy, the affected area is numbed with anesthetic and some or all of the tumor tissue is removed with a small knife.
* You will have extra imaging scans performed and used to see how the study drug combination may be affecting blood vessels that supply nutrients and oxygen to cancer. A DCE-MRI scan will be performed during the screening visit, at 24-48 hours after the start of Cycle 1, and at the end of Cycle 1. Like a regular MRI scan, the DCE-MRI scan involves passing part or all of the body into a long, narrow tube scanner that is open at both ends.

Study Drug Administration:

Bevacizumab and temsirolimus will be given in "cycles." Cycles will be about 21 days long or longer, depending on any side effects you may experience.

Bevacizumab is given by vein on Day 1 of each cycle. On Day 1 of Cycle 1, you will receive it over 90 minutes. If you tolerate it well in Cycle 1, you will receive it over 60 minutes in Cycle 2. If you tolerate it well in Cycle 2, you will receive it over 30 minutes in Cycle 3. It will continue to be given over 30 minutes in Cycle 4 and further cycles, as long as you still tolerate it well. Also, if the first dose is well tolerated, you may be given the remaining doses of Bevacizumab in the doctor's office in or near your hometown.

Temsirolimus is given by vein on Days 1, 8, and 15 of each cycle. During Day 1 of Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further cycles, as long you still tolerate it well. Also, if the first dose is well tolerated, you may be given the remaining doses of Temsirolimus in the doctor's office in or near your hometown.

Study Visits:

You will have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once between Days 7 and 14 during Cycle 1. During the rest of the cycles, you will have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once every 3 weeks. The status of the disease will be checked by a CT or MRI scan after every 2 cycles, starting after Cycle 2.

Length of Study Participation:

You may continue to receive additional cycles of the study drugs, unless the cancer gets worse or intolerable side effects occur. In that case, you will be taken off study.

Once your participation is over in this study, you will receive standard-of-care follow-up for the disease.

This is an investigational study. Bevacizumab and temsirolimus are commercially available. Bevacizumab is FDA approved for the treatment of colorectal cancer and a type of lung cancer. Temsirolimus is FDA approved for the treatment of kidney cancer that has spread. The combination of bevacizumab and temsirolimus is not FDA approved. At this time, it is being used in research only.

Up to 183 patients will take part in this study. All will be enrolled at MD Anderson.

Bevacizumab and Temsirolimus in Patients With Advanced Malignancy

A Phase I Trial of Bevacizumab and Temsirolimus in Patients With Advanced Malignancy

Maximum tolerated dose defined as the dose level below the dose at which two of six patients experience drug-related dose limiting toxicity in the first cycle.

Anti-tumor efficacy of each combination determined by objective response per RECIST and WHO criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
DCE-CT of Thoracic Tumors as an Early Biomarker for Treatment Monitoring in Comparison With Morphologic Criteria	NCT04708483	Cancer, Lung Perfusion Compu... Cancer Liver Metastatic Lung... Metastatic Live...	Extra DCE-CT sc...	18 Years -	Hyperfusion
Bevacizumab and Temsirolimus in Patients With Advanced Malignancy	NCT00610493	Advanced Cancer	Bevacizumab Temsirolimus Additional Bloo... Biopsy DCE-MRI Scan	-	M.D. Anderson Cancer Center
DCE-CT of Thoracic Tumors as an Early Biomarker for Treatment Monitoring in Comparison With Morphologic Criteria	NCT04708483	Cancer, Lung Perfusion Compu... Cancer Liver Metastatic Lung... Metastatic Live...	Extra DCE-CT sc...	18 Years -	Hyperfusion
Bevacizumab and Temsirolimus in Patients With Advanced Malignancy	NCT00610493	Advanced Cancer	Bevacizumab Temsirolimus Additional Bloo... Biopsy DCE-MRI Scan	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for dce

Every month we try and update this database with for dce cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for dce

Every month we try and update this database with for dce cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for dce cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.