Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Osteosarcoma

Sarcoma

Liposarcoma

Histiocytoma, Malignant Fibrous

Sarcoma, Ewing

Chondrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Ewing Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Protein Kinase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Clotrimazole

Miconazole

Antifungal Agents

Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.

Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified. The MTD dose was the standard dose of temsirolimus used for the remainder of the study. Dose modifications were based on protocol parameters for toxicities.

temsirolimus plus liposomal doxorubicin

David M Loeb, MD, PhD

The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma. A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.

The effectiveness of treatments for recurrent sarcomas is quite limited. One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.

Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma

Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas

Dose limiting toxicities in each dose cohort.

Number of days from day 1 of treatment until date of death from any cause.

Interval from Date of start of treatment to date of disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.

Number of participants who completed at least 2 treatment cycles with evidence of response. Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS

AUC was calculated using a single compartment model.

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.

Interval from start of treatment to disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression

Number of days after 2 cycles of treatment, until maximal response is observed.

Number of days until documentation of disease progression or date of death from other cause

Number of days from documented improvement to disease progression.

National Comprehensive Cancer Network

Wyeth is now a wholly owned subsidiary of Pfizer

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Single arm consists of temsirolimus (Torisel) plus liposomal doxorubicin (Doxil). Temsirolimus is administered IV in sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Temsirolimus may continue beyond 2 years.

temsirolimus plus liposomal doxorubicin: Patients will be treated with temsirolimus (Torisel) temsirolimus weekly by iv and with liposomal doxorubicin (Doxil) (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.

Temsirolimus Plus Liposomal Doxorubicin

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

David M. Loeb, M.D., Ph.D.

Temsirolimus 15 mg/m^2

Temsirolimus 20 mg/m^2

Temsirolimus 27 mg/m^2

Number of Subjects Who Experienced Dose-Limiting Toxicities

Part 1: Incidence of Dose Limiting Toxicities

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included. from both Phase I and Phase II of the study are included.

Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events.

Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study who were not taken off study for early toxicity were included. Two of the eighteen subjects who were treated at the MTD were excluded.

Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who completed at least 2 cycles of treatment with temsirolimus dose of 20 mg/m\^2 or 27 mg/m\^2 were assessed for radiologic response.

Temsirolimus 20 mg/m^2 and 27 mg/m^2

Only participants who completed at least 2 treatment cycles (14/18 participants) were included to assess this outcome measure.

Objective Response Rate

Temsirolimus- Parent Drug

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. Cmax of Sirolimus was calculated using a non-compartmental model.

Sirolimus- Active Metabolite

Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The number (N) evaluable participants is less than the number of participants from whom samples were collected due to inadvertent processing mishaps.

Maximum Observed Plasma Concentration (Cmax)

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single compartment model.

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single non- compartment model.

Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The analysis was per protocol. The number (N) evaluable samples is less than the number of collected samples due to inadvertent processing mishaps.

Area Under the Curve (AUC)

Clearance was calculated using a single compartment model.

Drug Clearance

All subjects who received at least one dose of temsirolimus at the MTD, 20 mg/M\^2 plus liposomal doxorubicin were included.

Subjects Who Received Temsirolimus MTD, 20 mg/m^2

Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study are included.

Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Although the original protocol specified that "time to maximal response" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Time to Response

Although the original protocol specified that "duration of response" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Duration of Response

Although the original protocol specified that "clinical benefit rate" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Clinical Benefit Rate

Cohort 1, Dose Level 3

Cohort 2, Dose Level 4

Cohort 3, Dose Level 5

Overall Study

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Collection of tumor and blood samples at T0 (surgery) and T1 (6 months follow-up) Tumor microenvironment and blood multi-omics analysis In-depth functional characterization of tumor microenvironment Cancer stem cells generation and drug testing Data integration by business intelligence and development of artificial intelligence-based prognostic markers

Collection of tumor and blood samples at T0 (surgery) and T1 (6 months follow-up) Tumor microenvironment and blood multi-omics analysis In-depth functional characterization of tumor microenvironment Cancer stem cells generation and drug testing Data integration by business intelligence and development of AI-based prognostic markers

Biological biomarker analysis

Quintino Giorgio D'Alessandris, MD, PhD

Roberto Pallini, MD, PhD

Q. Giorgio D'Alessandris, MD

Liverana Lauretti, MD

The study aims at:

1. Perform a multilayer analysis relying on tight integration of in-depth multi-omics approaches with clinical data to discover immune markers, with attention to age and sex differences, predicting prognosis and defining key life/environmental elements, to guide AI-driven personalised treatments and ensure improved care and QoL of glioblastoma patients.
2. To deepen glioblastoma knowledge through the study of glioblastoma stem cell cultures and to assess the sensitivity of glioblastoma stem cell cultures to a number of chemotherapeutics in different experimental conditions.
3. To create a comprehensive, stakeholder-generated guidelines for the ethical use of patient data for artificial intelligence-assisted prediction systems in glioblastoma, including an online, easily accessible patient information brochure to increase patient empowerment in the field.

Stem Cell Analysis, Omics (Including Immunomics) and Artificial Intelligence in Glioblastoma

Improving Personalised Glioblastoma Care by Stem Cell Analysis, Omics (Including Immunomics) and Artificial Intelligence Approaches

Immune omic markers, namely the tumor count of the different lymphocyte subtypes and of T-cell receptor subtypes, will be correlated with overall survival.

A questionnaire investigating lifestyle/environmental patients features, including dietary habits, will be developed. Questionnaire data will be correlated with overall survival.

Assessment of the in vitro sensitivity of patient-derived cancer stem cells to chemotherapeutics

Oslo University Hospital

Istituto Superiore di Sanità

Luxembourg Institute of Health

Hospital Donostia

University Medical Center Goettingen

National Research Council

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Digestive System Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antiemetics

Gastrointestinal Agents

Micronutrients

Hematinics

Vitamins

Fluorouracil

Cisplatin

Fursultiamin

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Fursultiamine 100mg tid, po Radiotherapy 36Gy/18Fx Chemotherapy will include Cisplatin and 5-FU. Cisplatin 60-75 mg/m2 on days 1 and 29 with standard prehydration and antiemetic therapy.

5-FU 600-1000 mg/m2day administered as a continuous intravenous infusion for 96 hours after completion of the cisplatin on days 1 through 4 and 29 through 32

Fursultiamine

Forn-Chia Lin, M.D., Ph.D.

Esophageal cancer is a common and fatal malignancy. It is the eighth most common incident cancer and the sixth leading cause of cancer death in the world. In Taiwan, esophageal cancer was newly diagnosed in 2199 patients and was the cause of 1507 deaths in 2011. Squamous cell carcinoma is the predominant histological tumor type, accounting for about 90% of the cases. Esophageal squamous cell carcinoma (ESCC) is an aggressive disease, characterized with extensive local growth and frequent metastases. Concurrent chemoradiotherapy (CCRT) with or without surgery is the treatment option for locally advanced ESCC. Further, target therapy is used in conjunction with CCRT and surgery in ESCC since several years ago. However, the therapeutic outcomes are not satisfactory due to the emergence of chemo-radioresistance. It is imperative to investigate new biomarkers and to find novel treatment targets in ESCC.

A small population of tumor-initiating cells or cancer stem cells (CSCs) possess some biological functions like normal stem cells, including self-renewal, asymmetric cell division, slowly proliferation rate and drug-resistance. CSCs from many primary tumors and cell lines express specific stem cell markers, including Oct4, Sox2, Nanog, CD133 (promimin-1), Nestin, CD44 ,CD24, ALDH (Aldehyde dehydrogenase) and c-Kit. There are many evidences that CSCs are responsible for tumor initiation, progression and metastasis. CSCs are also believed to have important roles in cancer recurrence due to their resistance to anti-cancer drugs and radiation. CSCs express high levels of ATP-binding cassette (ABC) transporters. ABC transporter can pump cytotoxic drugs out of cells and is one important mechanism of multidrug resistance in CSCs. In addition, CSCs have high reactive oxygen species (ROS) scavenger expression to remove ROS produced from irradiation therapy.

Fursultiamine (also known as thiamine tetrahydrofurfuryl disulfide, TTFD) is a derivative of vitamin B and currently used for nutrition supplement. The investigators have identified that Fursultiamine suppressed OCT-4, SOX-2, NANOG expression and decreased ABCB1 and ABCG2 in tumor sphere of ESCC cell lines. In this project, the investigators will conduct a prospective phase II study to investigate the effect of Fursultiamine combined with CCRT in ESCC patients. Stem cell markers in clinical specimens collected before and after CCRT will be evaluated.

Fursultiamine in Esophageal Squamous Cell Carcinoma Patients Who Receive Concurrent Chemoradiotherapy

To Study the Effect of Fursultiamine in Esophageal Squamous Cell Carcinoma Patients Who Receive Concurrent Chemoradiotherapy

National Cheng-Kung University Hospital

The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy. The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall. The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).

Tumor Biopsy via Ultrasound Endoscopy

Anthony Capobianco, MD

Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory suggests that most tumors undergo a process of differentiation through which a relatively rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result of this cellular diversity, one or more cells within the tumor are likely to be resistant to therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the original intervention. The cellular programs driving the uncontrolled proliferation of many solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs will be effective in the treatment of cancer. The investigator's research program focuses on the elucidation of signaling mechanisms, control of cellular processes and discovery of small molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental to CSCs. Our preliminary results identified a novel Notch associated protein NACK that functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human solid tumors and is required for cell survival and tumor growth in notch -dependent tumor cells.

The investigator's aim is to further interrogate the link between Notch and Nack.

Specific Aims:

* Identify and isolate the cancer stem cell populations from primary chemo naive esophageal tumor samples.
* Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in specific cell populations, such as the CSC.
* Determine the degree of cross-talk between these pathways and which of these pathways is essential for the self renewal properties and tumorigenic properties of the esc population.
* Identify critical targets for therapeutic intervention in CSC populations.

Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients

Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma	NCT00949325	Sarcoma	temsirolimus pl...	1 Year -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Stem Cell Analysis, Omics (Including Immunomics) and Artificial Intelligence in Glioblastoma	NCT05941234	Glioblastoma, I...	Biological biom...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Fursultiamine in Esophageal Squamous Cell Carcinoma Patients Who Receive Concurrent Chemoradiotherapy	NCT02423811	Cancer Stem Cel...	Fursultiamine	20 Years - 75 Years	National Cheng-Kung University Hospital
Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients	NCT02221245	Esophageal Canc...	Tumor Biopsy vi...	18 Years -	University of Miami
Fursultiamine in Esophageal Squamous Cell Carcinoma Patients Who Receive Concurrent Chemoradiotherapy	NCT02423811	Cancer Stem Cel...	Fursultiamine	20 Years - 75 Years	National Cheng-Kung University Hospital
Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma	NCT00949325	Sarcoma	temsirolimus pl...	1 Year -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Stem Cell Analysis, Omics (Including Immunomics) and Artificial Intelligence in Glioblastoma	NCT05941234	Glioblastoma, I...	Biological biom...	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Spots Global Cancer Trial Database for cancer stem cell