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The GcMAF 100 ng (Gc protein macrophage-activating factor) will be injected subcutaneously.

GcMAF injections (100 ng)

the placebo solution will be injected subcutaneously 100 ng.

placebo

This randomized, double-blind, placebo-controlled pilot study aims to evaluate the efficacy and safety of GcMAF in reducing nagalase levels and improving clinical outcomes in female patients with metastatic breast cancer over six months. Sixty patients will be randomized into two groups receiving either weekly GcMAF or placebo injections. The primary endpoint is the change in serum nagalase levels from baseline to six months. Secondary endpoints include clinical status, quality of life, adverse effects, and markers of inflammation and immune activity. Tumor response will be assessed using RECIST criteria, and quality of life will be measured with the EORTC QLQ-C30 questionnaire. Immune and inflammation markers will be evaluated using flow cytometry and ELISA. Adverse events will be monitored and categorized according to severity. Inclusion criteria include confirmed metastatic breast cancer, completion of one line of systemic therapy, adequate organ function, and elevated serum nagalase levels. The study will involve baseline measurements, monthly assessments, and final evaluations to compare changes in nagalase levels and other clinical outcomes between the GcMAF and placebo groups.

This randomized, double-blind, placebo-controlled pilot study aims to evaluate the efficacy and safety of GcMAF (Gc Macrophage Activating Factor) in female patients with metastatic breast cancer. The primary objective is to assess the reduction in serum nagalase levels, an enzyme associated with tumor activity, over a six-month period, and to evaluate improvements in clinical outcomes. The study involves 60 patients who will be divided into two groups: one receiving weekly injections of GcMAF and the other receiving a placebo.

Patients eligible for the study must have histologically or cytologically confirmed metastatic breast cancer, completed at least one line of systemic therapy, and have elevated serum nagalase levels. Additional inclusion criteria include female patients aged 18 to 70 years, ECOG performance status of 0 to 2, adequate bone marrow, liver, and renal function, and an estimated life expectancy of at least six months. Patients must also agree to use effective contraception and provide informed consent.

The primary endpoint is the change in serum nagalase levels from baseline to six months. Measurements will be taken at baseline, monthly, and at the end of the study using standardized enzymatic assays. Secondary endpoints include clinical status, assessed through objective tumor response using RECIST criteria and performance status using the ECOG scale, quality of life evaluated through EORTC QLQ-C30 questionnaires, immune activity measured by flow cytometry for various immune cell subsets, and inflammation markers such as CRP, interleukins, and TNF-alpha measured by ELISA. Adverse effects will be monitored weekly and categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

The study procedures include initial screening to measure baseline nagalase levels and assess eligibility, followed by randomization into the GcMAF or placebo groups. Patients will receive weekly injections for six months, with monthly assessments of nagalase levels, clinical status, quality of life, and blood samples for immune and inflammation markers. Interim assessments will occur at three months, with final assessments and data analysis at six months.

Exclusion criteria include the presence of other active malignancies, severe uncontrolled illnesses, pregnancy or breastfeeding, previous treatment with GcMAF, and known hypersensitivity to the study drug components. The study timeline consists of patient recruitment and baseline measurements in the first month, followed by six months of treatment and monitoring, with interim and final assessments and subsequent data analysis.

This study aims to determine if GcMAF can significantly reduce serum nagalase levels and improve clinical outcomes, including tumor response, performance status, quality of life, and immune and inflammation markers, in patients with metastatic breast cancer. The results will provide insight into the potential therapeutic benefits of GcMAF for this patient population.

Clinical Trial Protocol: Randomized Placebo-Controlled Pilot Study of GcMAF (Soloways TM) in Patients With Metastatic Breast Cancer

one of 4 categories Complete Response (CR), Partial Response (PR), Stable Disease (SD),Progressive Disease (PD)

(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire

Center of New Medical Technologies

S.LAB (SOLOWAYS)

Antineoplastic Agents

Immune Checkpoint Inhibitors

Immunomodulating Agents

Patients who has received mono-therapy of immune checkpoint inhibitor.

Patients who has received immune checkpoint inhibitor combining chemotherapy.

Clinical: A diagnostic model incorporating clinical variables (Age, Pathological diagnosis, level of serum tumor biomarkers etc.)

Clinical

Semantic: A diagnostic model incorporating semantic radiological features (shape, location, border, density etc.)

Semantic

Radiomic: A diagnostic model incorporating quantitative radiomic features (histogram, texture, morphology etc.)

Radiomic

Zhaoxiang Ye, M.D, Ph.D

This study aims to investigate the feasibility and efficiency of CT radiomic analysis which serves as a high through-put analytical strategy applied to image big-data resource in evaluating and predicting the response of immunotherapeutics. A multi-center retrospective diagnostic test has been designed for this aim to compare the predictive performance of clinical model, qualitative model incorporating semantic CT features and image-based quantitative radiomic model. The reference standard of therapeutic effect is determined by the latest evaluation result utilizing iRECIST within 365 days after recruited. This study intends to enroll 400 participates who had been diagnosed with advanced somatic solid tumor confirmed by histo- or cyto-pathological examination and were planning to receive immunotherapy.

Radiomics of Immunotherapeutics Response Evaluation and Prediction

Radiomics of Immunotherapeutics Response Evaluation and Prediction in Solid Tumor: A Multicenter Diagnostic Study

Area under curve (AUC) of each diagnostic model

Incidence of immune-related adverse events

Tianjin Chest Hospital

Shandong Tumor Hospital

West China Hospital

First Affiliated Hospital of Zhejiang University

Sun Yat-sen University

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Liaoning Tumor Hospital & Institute

Hubei Cancer Hospital

First Affiliated Hospital Xi'an Jiaotong University

Tianjin Medical University Cancer Institute and Hospital

Recurrence

Disease Progression

Participants will receive bintrafusp alfa.

Bintrafusp alfa

GSK Clinical Trials

The purpose of this study is to evaluate bintrafusp alfa in participants with metastatic or locally advanced urothelial cancer. This trial provides the first evaluation of bintrafusp alfa in participants with urothelial cancer that has progressed following platinum therapy.

A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer

A Phase Ib Trial to Evaluate the Efficacy and Safety of Bintrafusp Alfa Monotherapy in Metastatic or Locally Advanced/Unresectable Urothelial Cancer With Disease Progression or Recurrence Following Treatment With a Platinum Agent

IPD for this study will be made available via the Clinical Study Data Request site.

Confirmed overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.

Treatment emergent adverse events were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition. AEs which start or worsen on or after Bintrafusp alfa infusion are defined as treatment-emergent.

Merck KGaA, Darmstadt, Germany

GlaxoSmithKline

Safety population included all participants who were administered at least 1 infusion of bintrafusp alfa.

Participants with metastatic or locally advanced/unresectable urothelial cancer with disease progression or recurrence received intravenous (IV) infusion of 1200 milligram (mg) of bintrafusp alfa over 1 hour once every 2 weeks up to 79 weeks

Main Study - Bintrafusp Alfa

Participants with metastatic or locally advanced/unresectable urothelial cancer with disease progression or recurrence received intravenous (IV) infusion of 1200 milligram (mg) of bintrafusp alfa over 1 hour once every 2 weeks up to approximately 56 weeks.

PACT Phase - Bintrafusp Alfa

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

GSK Response Center

Confirmed Overall Response Rate (ORR) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Treatment Emergent AEs

Treatment Emergent SAEs

Number of Participants With Treatment Emergent Adverse Events (AEs) and Treatment Emergent Serious Adverse Events (SAEs)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

Number of Participants With Worst Grade Treatment Emergent AEs

Main Study (Up to Approx. 95 Weeks)

PACT Phase (Up to Approx. 56 Weeks)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasm Metastasis

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Frede Donskov, MD, DMSc, associate professor

Aska Drljevic-Nielsen, MD, ph.d-student

aska drljevic-nielsen, MD, ph.d-student

Frede Donskov, MD, DMSc, Associate Professor

Frede Donskov, MD, DMSc

The incidence of renal cancer in Denmark is approximately 900 new cases per year. Untreated, the 5-year survival rate for metastatic renal cancer (mRCC) is 2%. Development of angiogenesis inhibitors (AI) and check-point immunotherapy (CPI) has improved survival.

Treatment efficacy is evaluated by CT scans, using RESIST 1.1 (Response Evaluation Criteria in Solid Tumors). However, progressin in patients with mRCC treated with AI or CPI is difficult to characterize at the right time, using the RECIST 1.1. Therefore approximately 50 % of the patients are 'lost' to further treatment at the time of progression and die.

The investigators aim to evaluate if functional imaging parameters using spectral CT-techniques can detect treatment failure earlier, or more accurate, than routine CT. This could help us develop a new set of response evaluation criteria for functional imaging, giving a more precise assessment of treatment effect in patients with mRCC treated with AI and CPI.

Response evaluation criteria in metastatic renal cell carcinoma: Improved assessment of response and progression by Spectral CT?

Clinical Background

Renal cancer accounts for 2-3% of all cancers. The incidence of renal cancer in Denmark is approximately 900 new cases per year. Renal cell carcinoma (RCC) arises from the renal parenchyma and is by far the most common type. In 20-30% of all new cases, metastases exist at the time of diagnosis. Up to 25-50 % of patients treated with nephrectomy for localized RCC will eventually develop metastases. Untreated, the 5-year survival rate for metastatic RCC (mRCC) is 2%, and the median survival is 3 months. Within the last 10 years, an increased understanding of kidney cancer biology, and the immune system, has resulted in the development and approval of more than 12 new biological drugs. These are characterized by inhibiting the formation of new blood vessels (angiogenesis inhibitors) or by activating the patient's own immune system to attack the cancer disease (check-point inhibitors). Survival has significantly improved for the patient group with these drugs. The treatment results in control of tumor growth in the majority of patients, for a certain length of time, but should be given continuously, has side effects, and is expensive. In case of disease progression, treatment is changed to another drug. Thus, treatment for mRCC comprises sequential alternating drugs for as long as possible. However, progression is difficult to characterize at the right time and approximately 50 % of the patients are 'lost' to further treatment at the time of progression and die. The investigators therefore need improved diagnostic tools for early or more accurate detection of treatment failure, resulting in appropriate change of therapy at the right time. Routinely, treatment efficacy is evaluated by CT scans at baseline and every 3 months, using the criteria laid out in RECIST 1.1 (Response Evaluation Criteria In Solid Tumors). When interpreting the CT scan, the sizes of target lesions are measured, and an increase in the sum of target lesions by 30%, or the appearance of a new lesion, are interpreted as disease progression. However, the size of the tumor does not necessarily represent biological and physiological changes within the tumor; Tumors treated with angiogenesis inhibitors may show little or no change in tumor size, or may enlarge slowly during therapy, in spite of clinical benefit to the patient and extended time-to-progression. New lesions or tumor enlargement may be seen as part of pseudo-progression in patients treated with check-point inhibitors.

Therefore, the criteria from RECIST 1.1, despite being the best available at the moment, are far from an optimal tool for evaluating response and progression in patients with mRCC treated with biological therapy.

Recent studies from the research group behind the current pH.D. project have shown that functional imaging with Dynamic Contrast Enhanced Computer Tomography (DCE-CT) was able to measure changes in blood flow over time in a single metastasis. Using DCE-CT, the best clinical effect of angiogenesis inhibitor therapy was seen in patients with the greatest decline in blood volume and blood flow, measured after 1 month of treatment compared with baseline. In contrast, patients with low blood volume and low blood flow at baseline had the worst survival, with almost no benefit from treatment, regardless of whether they were treated with angiogenesis inhibitors or immunotherapy.

Based on these results, functional imaging using DCE-CT has the potential to serve as a predictive and prognostic tool in patients with mRCC. However, the DCE-CT technique can only measure functional parameters in one single metastasis and requires use of extra intravenous contrast, and increases radiation dose to the patient.

A new technique, Spectral CT, can visualize and measure functional parameters in all metastases in the body, with use of no extra intravenous contrast, and with no extra radiation dose compared to conventional CT. Spectral CT can quantify parameters such as iodine density and iodine concentration - parameters that could be associated with blood flow and blood volume - and also the relative atomic number can be measured. Response evaluation criteria in metastatic renal cell carcinoma: Improved assessment of response and progression by advanced CT-techniques?

Technical background

Spectral-CT adds spectral resolution to traditional CT scans through a new dual-layer spectral detector. With an Yttrium-based scintillator, the NanoPanel prism detector identifies high-energy and low-energy photons simultaneously, allowing not only anatomy, but also color to characterize the material's content of structures. This new technique allows the characterization of the metastases with parameters such as: iodine density, iodine concentration and the relative atomic number. Spectral CT uses iodinated contrast media -in the same dose as conventional CT. The amount of radiation in a Spectral CT is the same as in a conventional CT.

Aims and hypothesis The present study aims to evaluate functional imaging Spectral-CT as means to improve evaluation of response and progression in patients with mRCC.

The aim is to examine the correlation between Spectral-CT parameters and outcome in patients with mRCC treated with angiogenesis inhibitors and check-point inhibitor immunotherapy.

- Spectral-CT parameters at baseline have predictive and prognostic value, and spectral CT parameters during treatment are more accurate than RECIST 1.1 in determining response and progression.

Materials and Methods The project is an explorative prospective study, in which the investigators will examine the correlation between Spectral-CT functional imaging parameters and outcome in patients with mRCC treated with angiogenesis inhibitors and immunotherapy. CT will be performed at baseline, after 1 and 3 months and then every 3 months until progression or death. CT will be performed using the Spectral IQON scanner from Philips, from which the investigators will receive routine CT images, but also Spectral CT-images. In this way the patients can be their own control. The investigators plan to include 60 patients.

Endpoints and data processing In order to evaluate the accuracy of Spectral-CT imaging, the clinical endpoints best response, progression-free survival (PFS) and overall survival (OS) will be used.

Patient registry

Following patient information will be collected from the patients medical record og registered:

* Demographic data (date of birth, height, weight)
* Information about surgical and non-surgical treatment of renal cell carcinoma
* The patients list of medication
* Localisation of primary tumor and metastasis
* Histological parameters
* Findings on radiological examinations
* Blood tests: hemoglobin, white blood cell count, leucocytes, thrombocytes, creatinin, natrium, potassium, bilirubin, alanine transaminase, alkaline phosphatase, lactate dehydrogenase,calcium, albumine.
* Information about oncologic treatment after the patient progresses in actual study

Ethical Considerations The "Spectral-CT" study is approved by The Central Denmark Region Committees on Health Research Ethics (journal no. 1-10-72-242-17) and is approved the Data Protection Agency (journal no. 1-16-02-791-17). No procedure in the study will be performed before written informed consent has been obtained from each patient.

4. Perspectives Functional imaging using DCE and Spectral CT is considered a potential, new, non-invasive biomarker with the potential to serve as a predictive and prognostic tool. Biomarkers have traditionally been developed by analyzing blood or biopsy material. Core-needle tumor biopsies are, however, invasive procedures with associated discomfort and complications. The development of a non-invasive biomarker, obtained at the same time as routine CT assessment, which has potential for treatment selection (predictive tool) and improved prognostication, would therefore be a significant advance for patient with mRCC. To our knowledge no previous studies have investigated he correlation between DCE-CT parameters and the amount of blood vessels in tumor biopsies. Nor have Spectral CT been used as evaluation of response and progression in mRCC patients. The present study has the potential to develop an updated RECIST - integrating tumor size with functional information. This could give a more precise assessment of oncological treatment, thereby improving patient care.

Improved Assessment of Response in Metastatic Renal Cell Carcinoma Using Spectral-CT

Response Evaluation Criteria in Metastatic Renal Cell Carcinoma: Improved Assessment of Response and Progression by Spectral-CT

PFS is the time from the initiation of therapy and until progressive disease or death, whichever comes first, assessed up to 60 months. If a patient does not progress, PFS will be censored at the time of last follow-up - assessed up to 60 months.

Overall survival is the time between the first day of treatment and the date of death or last follow-up - assessed up to 60 months.

Response will be categorized according to the criteria from RECIST 1.1: complete response, partial response, stable disease and progressive disease - assessed up to 60 months.

University of Aarhus

Consultant, Associate Professor

Digestive System Diseases

Carcinoma, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

John V Reynolds, MCh FRCS

A major focus of research in oncology is to identify patients who, following induction therapy, have a complete pathologic response, presenting opportunities for novel trials, including extended therapy or non-operative approaches, in addition to identifying cohorts who are resistant to the neoadjuvant therapy. The current gold standard for determining response to CRT is pathological evaluation following surgical resection, in particular the Mandard Tumour Regression Grade (TRG) or some modification thereof. At this time, however, there is no preclinical early response or post-treatment biomarker, nor endoscopic or radiologic assessment that predicts pathologic response prior to surgical resection.The aim of this study is to determine the accuracy of CT-PET for prediction of histopathologic response and/or oncologic outcome for patients with esophageal cancer.

The Predictive Value of CT-PET in Esophageal Cancer

CT-PET for Prediction of Histopathologic Response, Nodal Status and Oncologic Outcome Following Neoadjuvant Chemoradiation for Esophageal Cancer

Mandard tumor regression grade, ypT, ypN stage

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial Protocol: Randomized Placebo-Controlled Pilot Study of GcMAF (Soloways TM) in Patients With Metastatic Breast Cancer	NCT06434077	Breast Cancer	GcMAF injection... placebo	18 Years - 80 Years	S.LAB (SOLOWAYS)
Radiomics of Immunotherapeutics Response Evaluation and Prediction	NCT04079283	Solid Tumor Predictive Canc...	Clinical Semantic Radiomic	18 Years -	Tianjin Medical University Cancer Institute and Hospital
A Study to Evaluate the Efficacy and Safety of Bintrafusp Alfa (M7824) Monotherapy in Metastatic or Locally Advanced Urothelial Cancer	NCT04349280	Neoplasms	Bintrafusp alfa	18 Years -	GlaxoSmithKline
Improved Assessment of Response in Metastatic Renal Cell Carcinoma Using Spectral-CT	NCT03616951	Renal Neoplasm ... Response Evalua...		18 Years -	University of Aarhus
The Predictive Value of CT-PET in Esophageal Cancer	NCT02385604	Esophageal Neop...		18 Years -	St. James's Hospital, Ireland
The Predictive Value of CT-PET in Esophageal Cancer	NCT02385604	Esophageal Neop...		18 Years -	St. James's Hospital, Ireland

Spots Global Cancer Trial Database for response evaluation criteria in solid tumors