Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

A single measurement of serum squamous cell carcinoma antigen level is performed in the eligible Head and Neck squamous cell carcinoma patients.

The study tool measuring serum squamous cell carcinoma antigen level is ARCHITECT SCC (Abbott).

The gross tumor volume in the cross sectional imaging obtained within 2 weeks of each patient is calculated with the typical ellipsoid formula.

Non-interventional study

Correlation between serum squamous cell carcinoma antigen level and tumor volume in Head and Neck Cancer is to determine a correlation between level of serum squamous cell carcinoma antigen and tumor volume in Head and Neck Caner measured by cross-sectional imaging.

The study is a cross-sectional study. A single measurement of serum squamous cell carcinoma antigen level is performed in the eligible Head and Neck squamous cell carcinoma patients.

The study tool measuring serum squamous cell carcinoma antigen level is ARCHITECT SCC (Abbott).

The gross tumor volume in the cross sectional imaging obtained within 2 weeks of each patient is calculated with the typical ellipsoid formula.

Correlation between both parameters will be determined.

Serum Squamous Cell Carcinoma Antigen Level and Tumor Volume in Head and Neck Cancer

Correlation Between Serum Squamous Cell Carcinoma Antigen Level and Tumor Volume in Head and Neck Cancer

Prince of Songkla University

Assistant Professor

Nervous System Diseases

Rare Diseases

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Anti-Dyskinesia Agents

Cardiotonic Agents

Temozolomide

Lomustine

Amantadine

Antiparkinson Agents

Antiviral Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Analgesics, Non-Narcotic

This cohort of patients will be asked to orally ingest 200mg dose of FDA approved drug amantadine hydrochloride. This will be done at the following timepoints:

1. Within 4 weeks of the start of treatment; but as close to commencement of treatment (Day 1 of radiotherapy) as possible for newly diagnosed patients.
2. Cycle 1, Day 1 of chemotherapy (temozolomide or lomustine) +/- 7 days
3. Day 1 +/- 7 days for each visit where MRI is obtained (typically every 8-12 weeks - pre-cycles 4, 7, 10, for temozolomide or pre-cycles 3, 5, and 7 for lomustine)

Patients who are eligible for the study will be administered a regular 200 mg dose of FDA approved drug amantadine. This will be done at the following timepoints:

1. Within 4 weeks of the start of treatment; but as close to commencement of treatment (Day 1 of radiotherapy) as possible for newly diagnosed patients.
2. Cycle 1, Day 1 of chemotherapy (temozolomide or lomustine) +/- 7 days
3. Day 1 +/- 7 days for each visit where MRI is obtained (typically every 8-12 weeks - pre-cycles 4, 7, 10, for temozolomide or pre-cycles 3, 5, and 7 for lomustine)

Amantadine Hydrochloride

Anmol Mann, BSc.

Gary Annable

Marshall Pitz, MD, FRCPC

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The strikingly poor survival for patients with GBM (average survival 14-16 months following diagnosis) is due in part to limited early detection methods and an absence of effective therapeutic options. The study proposed would establish important evidence for the use of Health Canada approved drugs such as amantadine as a safe, effective and affordable way to monitor GBM. The method is based on the overproduction of a key enzyme in GBM cells called spermine/ spermidine n-acetyl transferase (SSAT1). The increased SSAT1 expression in GBM results in increased metabolism of the drug which is detected in the blood or urine of patients with GBM. The levels of acetyl-amantadine captured will be correlated with the tumor burden as seen on the MRIs of these patients. Thus, the study aims to determine the usefulness of amantadine as a diagnostic biomarker for GBM.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with a median age of onset of 55 to 60 years. Most patients are treated with postoperative radiation and chemotherapy following their initial surgery. For newly diagnosed, high grade gliomas, the first post-radiation cycle of temozolomide (an oral chemotherapy drug) typically begins four weeks after completion of radiation therapy1. During radiation, temozolomide or lomustine is given daily (seven days per week). Assessment of response and progression is made through brain magnetic resonance imaging (MRI) with contrast, which is typically obtained within one month after completion of radiation therapy and then every two months during adjuvant temozolomide to assess disease status1. With the available standard of care, the median overall survival of patients with glioblastoma remains very low - approximately 10 to 12 months2.

The poor prognosis with GBM is a result of an absence of early detection and ineffective treatment options. The proposed exploratory pilot project attempts to addresses the problem of accurate tumor progression monitoring in GBM through the development of a drug biomarker that monitors spermidine/spermine N1-acetyltransferase (SSAT1) activity. SSAT1 is an important enzyme involved in polyamine regulation in the cell. As polyamines are essential for tumor proliferation, SSAT1 is over-expressed in many different cancers, as shown in a number of non-clinical trials3,4,5. These trials provide a rationale for our project: if SSAT1 is overexpressed in cancers including glioblastoma, then a substrate of SSAT1 could serve as a biomarker for determining the cellular activity of SSAT1. An effective substrate is amantadine, and following its acetylation by SSAT1, N-acetyl-amantadine levels excreted in the blood and urine samples of patients with glioblastoma could be used to indicate the presence of upregulation of SSAT1, and therefore, indicative of cancer. Recently published clinical trials involving investigators here at University of Manitoba and CancerCare Manitoba have reported a method for assessing tumor progression in lung and breast cancer patients based on acetyl- amantadine levels in blood and urine6,7,8. The assay is predicated on the selective acetylation of the drug amantadine by SSAT1. Published studies indicate increases in acetyl-amantadine in blood and urine from patients receiving a single oral dose of amantadine was predictive of tumor burden. Tappia et.al.7 reported that human cancer is associated with high urinary concentration of acetyl-amantadine with receiver-operating characteristic (ROC) for acetyl-amantadine demonstrated to be 0.689 (CI: 0.591-0.786, 95%) in lung cancer and 0.717 (CI: 0.577-0.858, 95%) for breast cancer.

Given the use of acetyl-amantadine as an early biomarker for lung and breast cancer, the present study protocol examines the extent to which acetyl-amantadine levels in blood and urine can be used to detect glioblastoma progression, particularly tumor recurrence which happens in the majority of patients and is considered inevitable after a median survival time of 32 - 36 weeks1. There are currently no studies that have attempted to determine the diagnostic value of acetyl-amantadine in glioblastoma patients, and therefore, this would be a pilot project. Under this protocol, patients diagnosed with glioblastoma (newly or recurrent) who are following the standard of care (surgical resection and radiation/chemotherapy) will be enrolled in the study. An initial assessment of the participant's baseline acetyl-amantadine levels in blood will be determined at the first visit. Thereafter, participants will be administered a standard 200 mg dose of the Health Canada approved drug amantadine at every visit in which MRI based imaging assessments are being performed (typically, every 8 - 12 weeks). Blood and urine samples will be taken at each visit to assay for acetyl-amantadine levels. These resulting acetyl-amantadine levels will be correlated with MRI based image findings to determine the extent to which this biomarker can be used for treatment monitoring in glioblastoma patients.

While the hypothesis is that acetyl-amantadine levels in blood or urine can be used to track tumor progression, an increase in acetyl-amantadine level would not indicate per se what type of tumor was present. For this reason, a metabolic profile on blood and urine samples collected from glioblastoma patients will be performed, to determine if there is a metabolic signature that can be established for glioblastoma.

All patients eligible for the study who have provided consent will be asked to ingest a regular 200mg dose of FDA approved drug Amantadine, according to timelines proposed in the protocol.

Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma

Samples of plasma and urine will be analyzed by established analytical methods (as developed by Biopharmaceutical Research Inc., Vancouver, B.C.; Health Canada and FDA approved). Quantitative analysis of amantadine and acetyl-amantadine in plasma and urine samples will be performed using liquid chromatography triple quadrupole tandem mass spectroscopy (LC-MS/MS). Samples (50 µl) will be spiked with 50 µl of internal standard, deuterated acetyl-amantadine (d3-Ac-amantidine), and proteins precipitated with 0.5 ml of ice-cold methanol. The lyophilized deproteinated samples are reconstituted in 0.1 ml of 0.1% formic acid. Samples are injected onto a C-18 stationary column and eluted using a gradient mobile phase consisting of 0.1% aqueous formic acid (A) and 0.1% formic acid in methanol (B). The run time for each sample is 9 minutes with the mobile phase starting at 5% B and increasing to 95% B during sample elution.

Standard of care MRI will be used. Definitions of response to standard therapy (progression, stable disease, response) will follow the established Response Assessment in Neuro-Oncology (RANO) guidelines9.

Post-hoc volumetric analysis will be done using quantitative semi-automated Olea Sphere software (Olea Medical, France).

The study does not require additional MRI scans to be performed; Routine MRI images, as per glioblastoma standard of treatment, are posted to Radiology Information System/Picture Archiving and Communication System (RISPACS) and will be accessed for analysis.

University of Manitoba

The Metabolomics Innovation Centre

BioMark Diagnostics Inc.

Canadian Institutes of Health Research (CIHR)

CancerCare Manitoba

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Inoperable stage III (A and B) non-small-cell lung cancer (NSCLC) with indication for radical radiotherapy.

Christian Ostheimer, MD

The aim of the study is to retrospectively monitor the 'gross tumor volume' (GTV) before initiation of radiotherapy and its changes during radiotherapy and to correlate them with retrospectively recorded patient data, as well as with prognostic and therapeutic outcome after definite radiotherapy of locally advanced NSCLC in stage UICC III.

The prognostic relevance of the 'gross tumor volume' (GTV) in radiotherapy of advanced non-small-cell lung cancer (NSCLC) in stage III is adressed in a limited number of studies in the literature. The review article by Dubben et al., that comprises data until 1998, highlights the GTV as an important indicator and influencing factor for the therapeutic success after radiotherapy, albeit not being dominant over the T-stage (Dubben et al. 1988). In general, an increase in tumor volume correlates with a higher T-stage (Martel et al. 1997), but no congruence can neccessarily be assumed between the tumor volume and the T-determinator. Since the TNM-classification is primarily surgical however, it also does not provide sufficient information for prognosis when surgical therapy is not the first choice.

Available evidence suggests that the GTV in particular at the beginning of therapy acts as a statistically significant prognostic indicator regarding overall survival and / or local tumor control (Martel et al. 1997; Bradley et al. 2002; Basaki et al. 2006; Etiz et al. 2002; Werner-Wasik et al. 2001; Wer-ner-Wasik et al. 2008; Stinchcombe et al. 2006; Dehing-Oberije et al. 2008; Willner et al. 2002; Ball et al. 2013). A direct comparison between different studies is, however, often hampered due to the large variation of measurement time points during therapy, as well as the employed definition of the tumor volume. For example, all studies include patients whose GTV was determined after (neoadjuvant) chemotherapy. In addition, three studies even combine the tumor volume of the primary tumor with affected lymph nodes (Etiz et al. 2002; Werner-Wasik et al. 2008; Dehing-Oberije et al. 2008). Furthermore, no agreements can be found in the literature concerning volume changes during therapy. Nonetheless, all studies report a volume reduction at the end of therapy, albeit not always significant. In a study containing 10 patients treated with helical Tomotherapy, the authors observed a relative median tumor reduction during therapy of 1.2% per day (0.6-2.3%) (Kupelian et al. 2005).

The response of NSCLC to radiotherapy with or without chemotherapy is slow (Woodford et al. 2007) with tumors reaching their maximum response or minimal volume after 5-11 months after exposure (Werner-Wasik et al. 2001). If the tumor volume is determined too early, i.e. directly after the end of therapy, the results can lead to misinterpretation resulting in an overestimation of the tumor volume or correspondingly an underestimation of the therapeutic response (Siker et al. 2006). According to Bell et al., the predictive value of tumor volume changes in the first 18 months after radiotherapy is of particular importance. During this time, a significantly increased mortality was observed for larger tumor volumes.

Incorporation of a PET/CT in the context of the radiaton plan is advantageous with respect to the precise traget-volume definition and sparing of risk organs (Ruysscher et al. 2005; Nestle et al. 2006; Lavrenkov et al. 2005; van Baardwijk et al. 2007; Edet-Sanson et al. 2012; Ruysscher und Kirsch 2010; As-hamalla et al. 2005; Bradley et al. 2004; van Baardwijk et al. 2006; Vanuytsel et al. 2000). The superiority of PET compared to stand-alone CT was also shown in two meta-analysis (Gould et al. 2001; Gould et al. 2003). The importance of the 'standardized uptake value' (SUV) or the metabolic tumor volume (MTV) as well as the change in these parameters during radiotherapy has been repeatedly demonstrated (Berghmans et al. 2008, Gillham et al. 2008; Zhang et al. 2011; van Elmpt et al. 2012; Edet-Sanson et al. 2012; van Baardwijk et al. 2007; Vera et al. 2014; Vanuytsel et al. 2000; Feifei Na et al. 2014; Lopez Guerra et al. 2012; Lee et al. 2007; Lee et al. 2012; Huang et al. 2011; Xiang et al. 2012). These studies show partly a statistically significant correlation between tumorale FDG-accumulation before, during or after radiotherapy, or the decreasing accumulation during radiotherapy, respectively, and the overall survival. The results, however, suffer from a large uncertainty regarding the distinct influence corresponding to the SUV. Other studies report a significantly weaker association of the SUV and survival (Hoang et al. 2008; IKUSHIMA et al. 2010; Lopez Guerra et al. 2012). Due to the dynamic variations in the SUV and MTV during radiotherapy, a change in the prognostic validity during radiotherapy can be assumed. According to van Elmpt and others, the FDG uptake during the second (van Elmpt et al. 2012; Zhang et al. 2011) or fifth week of exposure is crucial for survival (Edet-Sanson et al. 2012). Work by van Baardwijk et al. shows an increase in the SUV in some patients during the first week of therapy, which is explained by radiation-triggered inflammation and tumor-biological changes due to radiotherapy (van Baardwijk et al. 2007). The results demonstrate that the appearance of tumor necrosis during radiotherapy or changes in the metabolic tumor situation or oxygenation affect the SUV parameter crucially (Hoang et al. 2008, Huang et al. 2014; Huang et al. 2011). In this context, tumorhypoxia and the corresponding effects on the metabolism of glucose are of particularly importance: A hypoxia-simulated upregulation of the membranic glucose transporter with consecutive increase of cellular FDG uptage can lead to a false SUV value, calling for a combination of SUV or MTV with other prognostic parameters as well as hypoxia-specific imaging (FMISO-PET) (Ikushima et al. 2010, Berghmans et al. 2008). Consequently, the optimal timevpoint for carrying out a PET during / after radiotherapy is not well defined, especially when the protracted tumor response after completion of radiotherapy is taken into account, leaving the integration of additional PET measurements during radiotherapy exclusively to clinical studies.

In conclusion, evidence from available literature regarding the prognostic and predictive value of tumor volume before and particularly its changes during radiotherapy of locally advanced NSCLC is conflicting and inconclusive. Currently available studies often include only a small number of patients with partly overlapping patient cohorts. Current data is additionally limited due to the highly heterogeneous GTV detection time points as well as the definition and detection methodology of tumor volumes.

Based on the observation that a significant tumor volume reduction occurs during radiotherapy, a reevaluation of the tumor volume during radiotherapy could allow an adaptation of the target volumes with dose escalating in the tumor area, while at the same time, improving the protection of organs at risk.

The prognostic or predictive significance of absolute tumor volumes or their change under radiotherapy is to be evaluated multicentrically and its integration into already existing prognostic models is to be multicentrically validated.

Prognostic Evaluation of Tumor Volume and Its Changes in Radical Radiotherapy of Advanced NSCLC

Multicentric Retrospective Prognostic Evaluation of Tumor Volume and Their Change in the Curative-intended, Radical Radiotherapy of Locally Advanced NSCLC

from the start of Radiotherapy until death / last seen during follow up

in ml (cc) as detected by initial planning CT or diagnostic CT before the start of RT

in ml (cc) as detected in re-planning CT or CBCT before initiation of radiation boost

percental increase / decrease of GTV in relation to basal GTV1

Radiation Oncology Working Group of the German Cancer Society

Martin-Luther-Universität Halle-Wittenberg

Gland and Hormone Related Diseases

Adenoma

Pituitary Diseases

Pituitary Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Pasireotide

Hormones

Hormone Antagonists

All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks

20 and 40 mg of powder in vials and 2 mL of vehicle in ampoules (for reconstitution) administered as a depot intragluteal IM (intramuscular) injection

Pasireotide LAR

Novartis Pharmaceuticals

This study assessed pasireotide LAR efficacy on patients with non-functioning pituitary adenomas concerning tumor growth.

Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma.

An Open-Label, Single Arm, Phase II Study to Evaluate the Efficacy and Safety of Pasireotide LAR on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24.

Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor.

The absence and presence of disease-related symptoms were reported by patients and recorded by the medical staff. Patients classified the symptoms according to a 5-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe

Hormone levels, including those of GH, IGF-1, and prolactin were evaluated by a central lab

Hormone levels, including those of growth hormone (GH),insulin-like growth factor 1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free thyroxine (free T4), and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab

Alpha subunit levels were determined at a central laboratory.

Age, Continuous

Sex: Female, Male

White/Caucasian ancestry

Black/African ancestry

Asian ancestry

Other

Race/Ethnicity, Customized

Body mass index (BMI)

Baseline participants met eligibility requirements and received at least 1 dose of study medication

Study Director

Evaluable participants required tumor volume assessment at baseline and at week 24

Percentage of Participants With Non-functioning Pituitary Adenomas (NFPA) Who Achieve Tumor Volume Reduction of at Least 20% After 24 Weeks (FAS)

Main Baseline

Main Week 4

Main Week 12

Main Week 24

number of participants with evaluable data varied across visits

Tumor Volume Main Phase (FAS)

Extension Week 48

Extension Week 72

Extension Week 96

Tumor Volume in Extension Phase (FAS)

Tumor Volume Change From Baseline in Main Phase (FAS)

Tumor Volume Change From Baseline in Extension Phase (FAS)

Tumor Volume Percent Change From Baseline in Main Phase (FAS)

Tumor Volume Percent Change From Baseline in Extension Phase (FAS)

Week 4

Week 12

Week 24

Percentage of Patients Achieving Tumour Volume Reduction in Main Phase (FAS)

Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Main Phase (FAS)

Percentage of Patients Achieving Tumour Volume Reduction in Extension Phase (FAS)

Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Extension Phase (FAS)

Headache Absent

Headache Mild

Headache Moderate

Headache Severe

Visual Disturbances Absent

Visual Disturbances Mild

Visual Disturbances Moderate

Visual Disturbances Severe

Fatigue Absent

Fatigue Mild

Fatigue Moderate

Fatigue Severe

Decreased libido Absent

Decreased libido Mild

Decreased libido Moderate

Decreased libido Severe

Decreased libido Very severe

Erectile dysfunction Yes

Erectile dysfunction No

Regular Menses Yes

Regular Menses No

Baseline

Week 48

Week 72

Week 96

number of participants varied across visits

Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS)

IGF-1

Prolactin

Mean GH and IGF-1 Hormone Levels During Main and Extension Phases (FAS)

ACTH

Estradiol

participants with evaluable data varied across visits

Mean ACTH and Estradiol Hormone Levels During Main and Extension Phases (FAS)

number participants with evaluable data varied across visits

Mean Cortisol Hormone Levels During Main and Extension Phases (FAS)

Mean LH and FSH Hormone Levels During Main and Extension Phases (FAS)

Testosterone

Free T4

Mean Testosterone and Free T4 Hormone Levels During Main and Extension Phases (FAS)

Mean TSH Hormone Levels During Main and Extension Phases (FAS)

Mean Alpha Subunit Levels in Main and Extension Phases (FAS)

Evaluable participants had to have 50% reduction

Percentage of Participants With Reduction From Baseline of Alpha Subunit ≥50% in Main and Extension Phases (FAS)

Main Phase

Extension Phase

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Serum Squamous Cell Carcinoma Antigen Level and Tumor Volume in Head and Neck Cancer	NCT02879968	Head and Neck C...	Non-interventio...	18 Years -	Prince of Songkla University
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma	NCT04530006	Glioblastoma Mu...	Amantadine Hydr...	18 Years -	CancerCare Manitoba
Prognostic Evaluation of Tumor Volume and Its Changes in Radical Radiotherapy of Advanced NSCLC	NCT03055715	Non Small Cell ...		18 Years - 100 Years	Martin-Luther-Universität Halle-Wittenberg
Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma.	NCT01283542	Non-functioning...	Pasireotide LAR	18 Years -	Novartis
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma	NCT04530006	Glioblastoma Mu...	Amantadine Hydr...	18 Years -	CancerCare Manitoba

Spots Global Cancer Trial Database for tumor volume

Every month we try and update this database with for tumor volume 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.