Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Hypoxia

Disease Progression

Acidosis

Acidosis, Lactic

Signs and Symptoms, Respiratory

Acid-Base Imbalance

Metabolic Diseases

The purpose of this study is to analyze the gene expression patterns associated with various microenvironmental stresses in tumors to understand their roles in tumor progression and treatment responses. To achieve this goal, we will perform gene expression analysis of the tumor samples collected from an IRB-approved study (IRB #: 4516-05-2R2) International Phase III Study of Chemoradiotherapy versus Chemoradiotherapy Plus Hyperthermia for Locally Advanced Cervical Cancer directed by Dr. Mark Dewhirst. We will correlate the gene expression signatures of different microenvironmental stresses with the measured physiological parameters to understand their role in tumor progression, treatment response and clinical outcomes.

Jen-Tsan Chi, Ph.D.

In the first part of the proposal, we will determine the cellular responses to various microenvironmental factors (such as lactosis, acidosis, hypoxia, glucose deprivation) in cultured epithelial cells (commercially obtained) making use of DNA microarray analysis. From the analysis of these microarray assays, we will obtain the gene signatures reflecting how cells respond to these environments stresses. These gene signatures will be used to analyze and annotate the gene expression patterns in the tumor samples and whether hyperthermia will affect the physiological parameters and the corresponding gene signatures.

In the second part of the proposal, we will work with Dr. Dewhirst to perform gene expression study of cervical cancer samples from a phase III, multicenter, randomized clinical trial (IRB 4516-05-2R2). The subjects will de-identified and we will not obtain directly the PHI of the subjects in this trial. Subjects will be randomized to chemoradiotherapy alone or chemoradiotherapy + hyperthermia. For subjects randomized to hyperthermia, heat treatments will be administered concurrently with chemotherapy once weekly during the course of external beam radiation. In the hyperthermia suite, catheters will be placed in the cervical os, vagina and rectum for internal temperature monitoring. Hyperthermia will be given externally to the pelvis and abdomen using the BSD Sigma 60 ,Sigma Eye or Sigma Ellipse systems. Initial power will be limited to less than 1500 watts with phase and amplitude adjusted for equal surface electric fields in each quadrant of the applicator. Heating will continue for 60 minutes after average cervical os or interstitial temperatures of 40°C have been achieved, or for a maximum total duration of 90 minutes, whichever is longest. The bolus temperature will be 37° at initiation of power and will be reduced as necessary for patient comfort and/or to help maintain oral temperature of 38.5C. Power will also be reduced or treatment will be stopped at the patient request, or due to intractable pain, nausea or vomiting, if normal tissue temperature rises to 44°C, pulse \> 160, BP \> 180/100 or \< 90/50, altered mental status, or systemic temperature \> 38.5°C.

A. The research materials will include the tumor biopsy obtained before and after HT treatments to be used for gene expression studies as well as for the IHC and ISH studies to the findings from our microarray analysis. We will also obtain the information on the tumor physiological parameters information measured in these tumors.

B. The data of the tumor physiological parameters measured and the response to treatments and other clinical outcomes of these patients will also be acquired.

C. Only the physicians taking care of the patients will have access to the patient identifies and other Protected Health Information (PHI). All information will be de-identified and remain anonymous during the studies.

D. The specimens will be collected when the patients undergo medical care for their respective diseases. No new materials or data will need to be collected specifically for this proposal. These biopsies and physiological measurements are included in the original proposed clinical trials.

The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression

The Gene Expression Studies of Tumor Microenvironments and Their Roles in Tumor Progression

Duke University

Neoplasms

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Stomach Cancer

Other Dietary Supplements

All Drugs and Chemicals

Omega 3 Fatty Acid

All patients received TPN for 5 days postoperatively, according to a standard protocol: 3 g/kg BW glucose (5% Dextrose in Ringer's Lactate, Biosel, Istanbul), 1.2 g/kg BW amino acids (Aminosteril 10%, Fresenius-Kabi) and 0.8 g/kg BW omega-6 fatty acids (Lipovenoes® 10%, Fresenius-Kabi) were provided to both groups through an indwelling central venous catheter. In the omega-3 group, the lipid content of TPN was replaced partially by omega-3 fatty acids (Omegaven®, Fresenius-Kabi) up to 0.2 g/kg BW per day.

All patients received TPN for 5 days postoperatively, according to a standard protocol: 3 g/kg BW glucose (5% Dextrose in Ringer's Lactate, Biosel, Istanbul), 1.2 g/kg BW amino acids (Aminosteril 10%, Fresenius-Kabi) and 0.8 g/kg BW omega-6 fatty acids (Lipovenoes® 10%, Fresenius-Kabi) were provided to both groups through an indwelling central venous catheter.

Lipovenoes® 10% and Omegaven®,

Pre- and intra-operative nutritional support in patient undergoing major surgery results in decreased morbidity and mortality. Studies investigating the role of omega-3 fatty acids in these patients are increasing. Some are focused on perfusion at the cellular level. This study was undertaken to address the effect of postoperative administration of omega-3 fatty acids on cellular hypoperfusion associated with major gastric surgery.

Impact of Omega-3 Fatty Acids on Lactate

Do Omega-3 Fatty Acids Have Any Impact On Serum Lactate Levels After Major Gastric Cancer Surgery?

Ege University

Skin and Connective Tissue Diseases

Nervous System Diseases

Breast Neoplasms

Metabolic Syndrome

Syndrome

Autonomic Nervous System Diseases

Primary Dysautonomias

Lipid Metabolism Disorders

Insulin Resistance

Hyperinsulinism

Glucose Metabolism Disorders

Menopause

Two cohorts of both healthy postmenopausal women and women free of postmenopausal breast cancer recurrence. Each of the groups will be split into two different exercise programmes. Both programmes, High Intensity Interval Training (HIIT) programme (metabolic power training) and Muscle Power Intervention (MPI) programme will consist of 8 weeks.

Two cohorts of both healthy postmenopausal women and women free of postmenopausal breast cancer recurrence.

Metabolic Power Training: A High Intensity Interval Training (HIIT) intervention, 3 times per week (30 min session) during 8 weeks with professional supervision and intensities adapted and modified during the intervention period.

HIIT program (8 weeks)

Muscle Power Intervention (MPI), 2 times per week (45 min session) during 8 weeks with professional supervision and intensities adapted and modified during the intervention period.

MPI program (8 weeks)

Cristina Blasco Lafarga, Tenured Professor

Cristina Blasco Lafarga, PhD

Jordi Monferrer-Marín, Predoctoral student

Ainoa Roldán, PhD

Jørn Wulff Helge, PhD

POWER Health is a randomized clinical trial with a two-arm parallel design whose objectives are 1) to study metabolic flexibility and autonomic function (both capacities that describe cardiovascular health) in a sample of postmenopausal oncological women vs postmenopausal untreated controls (CT); and 2) to analyze the impact of two different 8-week physical exercise supervised interventions: HIIT training vs strength training focused on muscle power, on both cardiovascular capacities in these populations.

Nowadays, breast cancer is the most common type of cancer worldwide, accounting for 30% of all cancers in Spanish women in 2023. Cancer is also the second leading cause of death in developed countries, following cardiovascular diseases, with which it shares a close relationship. Additionally, we know that the incidence of breast cancer increases with age, experiencing a rise after menopause. However, lifestyle and physical exercise are known to improve the prevention, prognosis, and survival of this disease, as well as enhance quality of life in these patients. Indeed, recent studies have highlighted the relevance of cardiovascular health in this oncological process, as well as the potential of physical exercise interventions to improve cardiovascular health following the disease.

POWER Health is a randomized clinical trial aimed at studying metabolic flexibility and autonomic health in a population of breast cancer recurrence-free women (RFC) compared to postmenopausal untreated controls (CT), along with the implementation of two supervised exercise interventions in both populations. These interventions will last for 8 weeks, one involving HIIT exercise focused on improving metabolic power (MPI), and the other one involving strength exercise focused on enhancing muscular power, with the hypothesis of better metabolic flexibility and autonomic function, and consequently, better cardiovascular health.

POWER health is a mixed method design: cross-sectional \& longitudinal study. Given the feasibility and simple application of POWER Health, this clinical trial will contribute to the prevention and improvement of the health of postmenopausal women, with an important clinical and economic impact, not only in the scientific community but also in clinical practice.

Metabolic Flexibility and Autonomic Control After Muscle Power vs Metabolic Power Training in Postmenopausal Oncological Women: the POWER Health Study

Postmenopausal Oncological Women Exercising for Recover Their Health. Associations and Changes in Metabolic Flexibility and Autonomic Control After Two Training Programs (Muscle Power vs Metabolic Power): the POWER Health Study

Fat oxidation rates calculated from VO2 and VCO2 values collected by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) and after applying Frayn's stoichiometric formulae, during an incremental test from 0.45 W/kg with 0.15W/kg each 4-min step

Non-linear mathematical variable that allows collecting physiological information and vagal activity of the organism, analysed in 2-minute intervals by Kubios Scientific software (Kuopio, Finland), during the incremental test

Calf, waist and hip circumferences will be assessed with an anthropometric tape measure (cm)

Body composition assessment will be obtained by bioimpedance (Tanita DC-430 MA S; Tokyo, Japan; kg)

The investigators will also assess systolic and diastolic blood pressure in the left (whenever possible) arm at rest.

The investigators will also assess oxygen saturation in middle finger of the right hand at rest.

The SARC-F will be used to evaluate the risk of sarcopenia

The International Physical Activity Questionnaire (IPAQ) will be used to evaluate the current physical activity level of the participants. Minimum value = 0 min/day of physical activity // Maximum value = 1440 min/day of physical activity. Higher scores imply a more physically active pattern.

Lactate assessment will be obtained by lactate analyzer (Lactate Scout Sport SensLab GmbH, Leipzig, Germany)

The Rating Perceived Exertion (RPE) of Borg scale will be used to obtain the perceived effort. Minimum value: 1 // Maximum value: 10. Higher scores mean a worse outcome.

The Visual Analogue Scale of Pain (VAS) scale will be used to obtain the local pain assessment. Minimum value: 1 // Maximum value: 10. Higher scores mean a worse outcome.

Cadence will be monitorized by the smart roller Saris H3 (CycleOps Hammer Direct Drive Trainer, Saris, Madison, USA).

Power will be monitorized by the smart roller Saris H3 (CycleOps Hammer Direct Drive Trainer, Saris, Madison, USA).

Power will be calculated by Power Frail App (Toledo, Spain)

Metabolic rate will be registered by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) in baseline conditions

Resting exchange ratio will be registered by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) in baseline conditions

Fat oxidation will be registered by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) in baseline conditions

Carbohydrate will be registered by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) in baseline conditions

Carbohydrate oxidation rates will be calculated from VO2 and VCO2 values collected by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) and after applying Frayn's stoichiometric formulae, during an incremental test from 0.45 W/kg with 0.15W/kg each 4-min step

Energy expenditure rate will be calculated will be collected by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) during an incremental test

FATmax will be calculated will be collected by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) during an incremental test

VO2peak will be calculated will be collected by indirect calorimetry (COSMED K5 portable metabolic analyzer, Rome, Italy) during an incremental test

Non-linear mathematical variable that allows collecting physiological information and parasympathetic activity of the organism, analysed in 3-minute intervals by Kubios Scientific software (Kuopio, Finland), during the incremental test

Linear mathematical variable that allows collecting physiological information and parasympathetic activity of the organism, analysed in 2-minute intervals by Kubios Scientific software (Kuopio, Finland), during the incremental test

Generalitat Valenciana

University of Valencia

Senior Lecturer

Adenocarcinoma

Inflammation

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

The patient will be evaluated for baseline clinical and laboratory values, and counselled on very low carbohydrate diet.

The patient will be evaluated for baseline clinical and laboratory values, and counselled on normal healthy .

1 : 4 ratio of carbohydrate to fat of the total daily calories intake

Very Low Carbohydrate Diet

Vicky S Budipramana, PhD

Fransiscus Arifin, MD

This study examine the effects of very low carbohydrate diet (in which the calories requirements are mostly from fat) to the level of systemic inflammation (measured by Glasgow Prognostic Score), serum lactate and TNF Alpha levels

This study examine the effects of very low carbohydrate diet (in which the calories requirements are mostly from fat) to the level of systemic inflammation (measured by Glasgow Prognostic Score), serum lactate and TNF Alpha levels. The subjects are colorectal adenocarcinoma patients who were decided by experts to be managed by best supportive care. These patients are not deemed to be suitable for surgical intervention , chemotherapy or radiotherapy anymore. The main treatment is supportive. We would like to examined the effect of very low carbohydrate diet on these patients, in which theoretically tumtor cells of the colorectal adenocarcinoma needed glucose to replicate and increases the systemic inflammation response.

Patients were randomized in to two groups, with very low carbohydrate diet and with normal diet

Care provider are not told whether the patient belongs to intervention or control group

Very Low Carbohydrate Diet Effects to GPS, Serum Lactate and TNF Alpha on Colorectal Cancer

Effect of Very Low Carbohydrate Diet to Glasgow Prognostic Score, Serum Lactate and TNF Alpha on Colorectal Cancer Patients With Best Supportive Care

A score to evaluate systemic inflammation response

Level of Tumor Necrosis Factor Alpha in the blood serum

Dr. Soetomo General Hospital

Blood and Lymph Conditions

Immune System Diseases

Infections

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Burkitt Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Day -7: single dose of 5 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 5 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965

Day -7: single dose of 10 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 20 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Day -7: single dose of 30 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 30 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Day -7: single dose of 30 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 15 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment (first 3 trial participants in the Expansion Cohort only; subsequent patients started treatment at Cycle 1, Day 1).

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Ruth Plummer, Prof

The main aims of this clinical study are to find out the maximum dose that can be given safely to patients, the potential side effects of the drug and how they can be managed and what happens to AZD3965 inside the body.

AZD3965 is a type of drug called a monocarboxylate transporter 1 inhibitor which is being used to stop the growth of cancer cells and kill cancer cells by blocking the action of one of the proteins involved in moving chemical compounds in and out of the cells of the body. This will be the first time that this type of drug has been given to patients.

The drug is a capsule and is taken daily. The study is in two parts. In Part 1 of the study, small groups of patients are treated at increasing doses to find the highest safe dose and best dose to give to patients in Part 2 of the study. It is planned that 40 patients will be entered into Part 1 of the trial.

In Part 2, the dose found to be safe in Part 1 is given to patients with diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL). It is planned that 20 patients will be entered into Part 2 of the trial.

Patients will need to visit the hospital weekly for two months and then every fortnight. Patients will have regular blood and urine tests, scans, heart traces and eye tests amongst other clinical tests. Research blood samples will also be taken to look at what happens to the drug inside the body. Treatment is planned to be given for up to 6 months, but patients benefiting from treatment will be able to keep having it for as long as they continue to benefit. It is important to explain that this is the first study of this drug and patients will have advanced cancer so it is unlikely that patients will benefit directly from taking part but the study may help improve future treatment of cancer.

Part 1 follows a rolling six dose escalation schedule of AZD3965 given once daily (OD) or twice daily (BD) until the maximum tolerated dose (MTD) is defined.

The recommended Phase II dose (RP2D) is based on the safety and pharmacokinetic (PK) results from Part 1.

All patients in Part 2 are treated at this RP2D to further explore the tolerability of this dose and schedule and to explore proof of principle of MCT1 inhibition in tumour types that were shown to express MCT1 and in which AZD3965 showed some effect pre-clinically (DLBCL and BL).

A Phase I Trial of AZD3965 in Patients With Advanced Cancer

A Cancer Research UK Phase I Trial of AZD3965, a Monocarboxylate Transporter 1 Inhibitor (MCT1) in Patients With Advanced Cancer

MTD was determined by testing increasing AZD3965 doses in Part 1 dose escalation cohorts (Cohorts 1-6) and defined as the total daily dose level below that at which ≥2 out of ≤6 evaluable patients had a dose-limiting toxicity (DLT) during Cycle 1 (including Day -7). DLTs were defined as highly probably/probably AZD3965 related haematological, cardiac, ophthalmic, other Grade 3/4 toxicity, death or drug-related toxicity causing AZD3965 interruption \>2 weeks (see protocol for specific criteria)

Number of patients who experienced protocol-defined DLTs (defined according to NCI CTCAE version 4.02). DLTs were defined as highly probably/probably AZD3965 related haematological, cardiac, ophthalmic, other Grade 3/4 toxicity, death or drug-related toxicity causing AZD3965 interruption \>2 weeks (see protocol for specific criteria)

A serious adverse event (SAE) is any AE, regardless of dose, causality or expectedness, that results in death, is life-threatening, requires in-patient hospitalisation or prolongs existing in-patient hospitalisation, results in persistent or significant incapacity or disability, is a congenital anomaly or birth defect or is any other medically important event. Any ophthalmic and/or cardiac DLT is considered a medically important event and therefore an SAE in this trial. Specific AE terms are provided in the Adverse Events section

A non-serious AE is any untoward medical occurrence that does not meet the serious criteria described for outcome measure 3 above. Specific AE terms are provided in the Adverse Events section

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. For twice daily dosing, Day -7 data reflect the full daily dose but subsequent timepoints reflect half the daily dose as PK sampling was conducted up to 12 hours following the first of the two daily doses; therefore, AUC is from 0 to 12 hours at those timepoints and is reported as a separate outcome measure.

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. AUC from 0 to 12 hours was applicable to twice daily dosing on Day 1 only. See AUC From 0 to 24 Hours Post AZD3965 Dosing for AUC for other cohorts and timepoints.

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method. For twice daily dosing, Day -7 data reflect the full daily dose and other timepoints reflect half the daily dose.

Plasma samples were analysed to determine the concentrations of AZD3965 using a previously developed LC-MS/MS method.

Plasma samples were analysed to determine the level of M30 using a validated cell death ELISA in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative.

Plasma samples were analysed to determine the level of M65 using a validated cell death enzyme-linked immunosorbent assay (ELISA) in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative.

Plasma samples were analysed to determine the level of nDNA using validated methodology in Part 1 (Cohorts 1-6). Assays not conducted for Part 2 of the trial as considered uninformative.

Antitumour activity measured according to RECIST version 1.1 (solid tumours)(see Eishenhauer et al; Eur J Cancer 2009, 45:228-247) or IWG criteria for Lymphoma (lymphoma)(see Cheson, Fisher et al; JCO 2014, 32:3059-3067). Complete or partial response/remission was confirmed by repeat measurements ≥4 weeks after response criteria were met; patients with stable disease met criteria at least once ≥6 weeks after first dose of AZD3965

AstraZeneca

Cancer Research UK

AE terms from vocabulary, NCI CTCAE V4.02 for Part 1 (AZD3965 Cohorts 1-6) and MedDRA V23.0 for Part 2 (Expansion Cohort)

AZD3965: Day -7: single dose of 5 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 5 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 1 (5 mg OD)

AZD3965: Day -7: single dose of 10 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 2 (10 mg OD)

AZD3965: Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 20 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 3 (20 mg OD)

AZD3965: Day -7: single dose of 30 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 30 mg AZD3965 OD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 4 (30 mg OD)

AZD3965: Day -7: single dose of 30 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 15 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 5 (15 mg BD)

AZD3965: Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment.

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Cohort 6 (10 mg BD)

AZD3965: Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment (first 3 trial participants in the Expansion Cohort only; subsequent patients started treatment at Cycle 1, Day 1).

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 BD orally for up to 6 28-day cycles.

Patients benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

AZD3965 Expansion Cohort (10 mg BD)

AZD3965: Day -7: single dose of 20 mg AZD3965 orally prior to start of continuous treatment (first 3 trial participants in the Expansion Cohort only; subsequent patients started treatment at Cycle 1, Day 1).

Cycle 1, Day 1: commenced dosing of 10 mg AZD3965 BD orally for up to 6 28-day cycles.

Trial participants benefitting from treatment could continue beyond 6 cycles for as long as they continued to benefit on agreement between the Investigator and the Sponsor.

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United Kingdom

Region of Enrollment

Lactate accumulation in peripheral blood mononuclear cells was originally a measure for assessment of the primary objective but the assay was confounded by methodological problems and high inter-patient variability. This measure was removed for Part 2 and not used for assessment of the primary objective. M30, M65 and nDNA assays are only quasi quantitative; data \>upper limit substituted with upper limit and data \<lower limit substituted with lower limit/2.

Regulatory Affairs Manager

All eligible participants recruited to dose escalation cohorts 1 to 6 who received at least one dose of AZD3965.

Part 1 Dose Escalation (Cohorts 1-6)

All patients recruited to dose escalation cohorts 1 to 6 who received at least one dose of AZD3965 (n=40)

MTD of AZD3965

All recruited patients who received at least one dose of AZD3965 (N=51)

Number of Patients Who Experienced DLTs

Number of Patients Who Experienced Serious AEs

Number of Patients Who Experienced Non-Serious AEs

Day -7

Day 1

Part 1: Eligible patients who received AZD3965 on Day -7 and had a baseline and post-dose sample analysed (N=32; could only be calculated for N=5 in Cohort 6 \[N=6 for some PK parameters\]); Part 2: Eligible patients who received AZD3965 on Day 1 and had a baseline and post-dose sample analysed (N=11). Only calculated for Day -7 and Day 1 in Part 1 and not calculated for other timepoints due to low number of samples or for Part 2 due to limited number of sampling timepoints.

Area Under the Concentration-Time Curve (AUC) From 0 to 24 Hours Post AZD3965 Dosing

AUC From 0 to 12 Hours Post AZD3965 Dosing

Day 29

Part 1: Eligible patients who received AZD3965 on Day -7 and had a baseline and post-dose sample analysed (N=33) (Only limited samples were available at Day 29); Part 2: Eligible patients who received AZD3965 on Day 1 and had a baseline and post-dose sample analysed (in Part 2 of the trial, PK data were only collected for Day 1)

Maximum Observed Plasma Concentration of AZD3965

Part 1: Eligible patients who received AZD3965 on Day -7 and had a baseline and post-dose sample analysed (N=33); Part 2: Eligible patients who received AZD3965 on Day 1 and had a baseline and post-dose sample analysed (N=11). Only calculated for Day -7 and Day 1 in Part 1; not calculated for other timepoints due to low number of samples or for Part 2 due to number of sampling time points. One patient in Cohort 6 did not have Day -7 data (N=5).

Time to Maximum Observed Concentration of AZD3965

Part 1: Eligible patients who received AZD3965 on Day -7 and had a baseline and post-dose sample analysed (N=32; one patient had a reduced dose in Cohort 6 at Day -7 so these data are not included in half life calculation). Not calculated for Part 2 due to limited number of sampling timepoints.

Elimination Half Life for AZD3965

Baseline

Day 8

All patients in Part 1 who received AZD3965 and provided pre and post-treatment blood samples (N=37). Some patients did not have data at all timepoints

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression	NCT00638040	Hypoxia Lactic Acidosis		18 Years - 50 Years	Duke University
Impact of Omega-3 Fatty Acids on Lactate	NCT00929461	Gastric Surgery	Lipovenoes® 10%...	25 Years - 65 Years	Ege University
Metabolic Flexibility and Autonomic Control After Muscle Power vs Metabolic Power Training in Postmenopausal Oncological Women: the POWER Health Study	NCT06336070	Breast Cancer F... Cardiometabolic... Metabolism Diso... Autonomic Dysfu... Cardiovascular ...	HIIT program (8... MPI program (8 ...	35 Years - 75 Years	University of Valencia
Metabolic Flexibility and Autonomic Control After Muscle Power vs Metabolic Power Training in Postmenopausal Oncological Women: the POWER Health Study	NCT06336070	Breast Cancer F... Cardiometabolic... Metabolism Diso... Autonomic Dysfu... Cardiovascular ...	HIIT program (8... MPI program (8 ...	35 Years - 75 Years	University of Valencia
The Gene Expression Studies of the Role of Tumor Microenvironments in Tumor Progression	NCT00638040	Hypoxia Lactic Acidosis		18 Years - 50 Years	Duke University
Very Low Carbohydrate Diet Effects to GPS, Serum Lactate and TNF Alpha on Colorectal Cancer	NCT03221920	Diet Modificati... Colorectal Aden... Systemic Inflam... TNF Alpha Lactate	Very Low Carboh...	18 Years - 65 Years	Dr. Soetomo General Hospital
A Phase I Trial of AZD3965 in Patients With Advanced Cancer	NCT01791595	Adult Solid Tum... Diffuse Large B... Burkitt Lymphom...	AZD3965 AZD3965 AZD3965 AZD3965 AZD3965 AZD3965 AZD3965	18 Years -	Cancer Research UK
Lactate Levels Correlates With Ki-67 in Brain Tumor Surgery	NCT03531307	Brain Tumor Anesthesia	Data correlatio...	-	Fundacion Clinic per a la Recerca Biomédica
A Phase I Trial of AZD3965 in Patients With Advanced Cancer	NCT01791595	Adult Solid Tum... Diffuse Large B... Burkitt Lymphom...	AZD3965 AZD3965 AZD3965 AZD3965 AZD3965 AZD3965 AZD3965	18 Years -	Cancer Research UK
Evaluation of Lactate in Patients Undergoing Glial and Non Glial Mass Surgery With Craniotomy	NCT04584827	Lactate Brain Tumor Post-Op Complic...	lactate level Glasgow Outcome...	18 Years -	Trakya University

Spots Global Cancer Trial Database for lactate

Every month we try and update this database with for lactate 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 lactate

Every month we try and update this database with for lactate 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 lactate 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.