Symptoms and General Pathology

All Conditions

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All Drugs and Chemicals

Rasburicase

As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed.

Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily

.15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed.

As Needed Rasburicase

Fixed Dose Rasburicase

Saroj Vadhan-Raj, MD

Primary Objectives:

To determine the efficacy of rasburicase administered as a single dose followed by as needed dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm) in the treatment of patients at high risk or potential risk for tumor lysis syndrome.

Secondary Objectives:

1. To evaluate the plasma uric acid area under the curve (AUC) from baseline through 7 days
2. To evaluate the incidence of renal insufficiency and electrolyte abnormalities.
3. To determine the safety and immunogenicity of rasburicase.
4. To evaluate the cost-effectiveness of the experimental treatment (investigational arm).

The Study Drug and TLS Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid in the blood may lead to decreased kidney function or kidney failure.

TLS occurs when high uric acid levels are caused by breakdown of tumor cells during the start of chemotherapy. The dead tumor cells can release uric acid and cause other symptoms of kidney failure, such as releasing large amounts of potassium and phosphorus (chemicals) into the blood.

Screening Tests Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study.

Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight.

Blood will be drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (using a sample from the routine blood draw) or urine pregnancy test.

Study Groups If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. There is an equal chance of being in either group.

Group A Participants in Group A will receive rasburicase by vein, over 30 minutes, on Day 1 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood. During Days 2-5 of Cycle 1 of chemotherapy, you will only receive rasburicase (once a day) if the levels of uric acid are high that day.

Group B Participants in Group B will receive rasburicase by vein, over 30 minutes, once a day from Days 1-5 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood.

Both Groups Treatment with rasburicase will only be given in Cycle 1 of chemotherapy. The chemotherapy will be given at least 4 hours (up to 24 hours) after the first dose of rasburicase.

Length of Study When your blood test results show that you do not have antibodies to rasburicase, your participation in this study will be over. You will be taken off this study if the TLS gets worse or intolerable side effects occur.

This is an investigational study. Rasburicase is commercially available, but it is not FDA approved for treating TLS. It is FDA approved for pediatric patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy that is expected to increase the blood levels of uric acid (the result of cancer cells dying from treatment). For treating TLS in adult patients, it has been authorized for use in research only. Up to 80 evaluable patients will take part in this study. All will be enrolled at M. D. Anderson.

Rasburicase in Patients at Risk for Tumor Lysis Syndrome

Phase 2 Study of Rasburicase Administered by Two Different Schedules (Fixed Dosing vs. As Needed Dosing) in Patients at High Risk or Potential Risk for Tumor Lysis Syndrome

Plasma UA response is defined as normalization of plasma UA levels within 48 hours after the start of study drug (rasburicase) and maintaining within the normal range after the final drug infusion on day 5. Plasma samples for UA were collected at baseline before rasburicase, 4- and 24-hours post-rasburicase, and daily during treatment.

Sanofi

M.D. Anderson Cancer Center

Group A: Single Dose

Group B: Daily Dose

Total

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Saroj Vadhan-Raj, MD / Professor

Number of Participants With Plasma Uric Acid (UA) Response

Overall Study

Neoplasms by Histologic Type

Hematologic Diseases

0.15mg/kg intravenously over 30 minutes once per day for 5 consecutive days.

Saroj Vadhan-Raj, M.D.

Primary

1. To determine the pharmacokinetic (PK) parameters of rasburicase in adult patients with leukemia and/or lymphoma at high risk or potential risk of tumor lysis syndrome (TLS)

Secondary

1. To evaluate plasma uric acid AUC from baseline (within 4 hours prior to first rasburicase treatment) through 48 hours after the last per-protocol planned administration of rasburicase treatment;
2. To evaluate the safety of rasburicase in adult patients with leukemia and/or lymphoma.
3. To evaluate incidence, duration, and type of immune responses (IgG, IgE, and neutralizing antibody) to rasburicase.

Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid may lead to reduced kidney function or kidney failure.

TLS occurs when high uric acid levels are caused by breakdown of tumor cells after the start of chemotherapy. The dead tumor cells can release uric acid and other symptoms of kidney failure, such as excessive amounts of potassium and phosphorus, into the blood.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Your complete medical history will be recorded, and you will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have blood drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (a sample will be used from the routine blood draw) or urine pregnancy test.

If you are found to be eligible to take part in this study, you will receive rasburicase by a needle in your vein over 30 minutes once a day for 5 days in a row. You will receive chemotherapy within 4-24 hours after your first dose of rasburicase.

On Days 1-5 (study drug treatment period), you will have a physical exam, including measurement of your vital signs. During this time, you will have blood drawn (about 2 tablespoons each) once a day for routine tests.

You will have blood drawn (less than 1 teaspoon each) for PK testing at different time points throughout this study. PK tests measure the level of the study drug in the blood at different times. You will have a total of 14 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 30 minutes and at 4, 8, 24, 48, 72, 96, 96.5,100,104,120 (Day 6),168 (Day 8), and 336 (Day 15) hours after your dose of the study drug.

You will have blood drawn (less than 1 teaspoon each) to measure the level of uric acid in your blood at different time points throughout this study so that researchers can learn the effectiveness of the study drug on your disease. You will have a total of 7 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 4, 24, 48, 72, 96,120 (Day 6), and 144 (Day 7) hours after your dose of the study drug.

You will also have blood drawn (less than 1 teaspoon each) for antibody testing at different time points throughout this study. Antibody testing is a method to check for proteins (IgG) made by your body that show that your body is reacting to rasburicase. You will have at least 5 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then on Day 14, Day 35, and at 3 and 6 months after your dose of the study drug.

If you have a positive IgG (antibody protein) at the 6-month blood draw for antibody testing, you will continue to have blood drawn (less than 1 teaspoon) every 6 months until your antibody protein is negative.

If you experience any side effects related to allergic reactions during treatment with the study drug (up to 30 days after your last dose of the study drug), you will have an additional blood draw (less than 1 teaspoon) for antibody testing within 48 hours after having the reaction.

You will be taken off this study if your disease gets worse or you experience any intolerable side effects.

You will have assessments after the end of your study drug treatment (from Days 1 to 5). These assessments will include a physical exam, including measurement of your vital signs, on Days 14 and 35. You will also have blood drawn (about 2 tablespoons each) for routine tests on Days 8 and 14.

This is an investigational study. Rasburicase is authorized by the FDA for use (in adults) in research only. Rasburicase will be provided free of charge during this study. Up to 20 patients will take part in this multicenter study. Up to 20 can be enrolled at M. D. Anderson.

Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS

Pharmacokinetic Evaluation of Rasburicase Dosed for 5 Consecutive Days as Uricolytic Therapy in Adult Patients With Leukemia and/or Lymphoma at High or Potential Risk of Tumor Lysis Syndrome (TLS)

Hematologic Neoplasms

Febuxostat

Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days

Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days

Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg)

Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg)

Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg)

Intervention is orally administered to patients in this arm.

Franco Locatelli, Prof, MD

The purpose of this study is to compare the exposure of febuxostat in pediatric patients (≥6\<18 years of age) and in adults suffering from hematological malignancies at intermediate to high risk of TLS and to compare the effect in terms of serum uric acid levels.

In the FLORET study it is planned to enroll 3 groups of patients in order to receive oral administration (film-coated tablets) of two different dose levels of febuxostat: children (from 6 to less than 12 years of age) will receive two different dose levels respectively; adolescents (from 12 to less than 18 years of age) will receive 80 and 120 mg/day respectively and adults (equal or major than 18 years of age) will receive 120 mg/day. The two dose levels for children and adolescents groups were to be sequentially administered, whereas the groups that will receive the first dose levels will simultaneously start the treatment at the study beginning. The individual treatment duration will be of 7 to 9 days, according to chemotherapy duration, as per Investigator's judgement.

Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults

Open Label, Multi-centre, Parallel Group Study to Compare the Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of Febuxostat Between Pediatric Patients (≥6<18 Years of Age) and Adults

Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)

Assessment of LTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). LTLS is diagnosed if levels of 2 or more values of uric acid, potassium, phosphate or calcium are more than or less than normal at presentation or if they change by at least 25% from baseline.

Assessment of CTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). CTLS is present when LTLS is accompanied by at least one of the following significant clinical complications: increased creatinine level ≥ 1.5 upper limit of normal, cardiac arrhythmia/sudden death or seizure.

Assessment of incidence, severity (through Mild/Moderate/Severe scale), seriousness and treatment-causality of TESS from Screening Visit to End of Study Visit. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event was considered as TESS if it occured for the first time or if it worsened in terms of seriousness or severity after first study drug intake.

Number of participants affected by TESS from Screening Visit to End of Study Visit.

Quality of life was to be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale was to be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale was to be used for patients aged less than 16 years. Both scales range from scores of 0 to 100 points at intervals of 10 where 0 points represent the worst outcome (KPS: 0 = death; LPS: 0 = unresponsive) and 100 points the best (KPS: 100 = normal, no complaints, no evidence of disease; LPS: 100 = fully active).

Menarini Group

Adverse Events were collected during Screening, i.e. after ICF signature until DAY 1, Visit 1 before first IMP intake and specifically Treatment Emergent Signs and Symptoms (TESSs) occurring from first IMP intake at Visit 1, DAY 1 until Visit 10, DAY 14.

Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days

Febuxostat: Intervention is orally administered to patients in this arm.

Cohort 1

Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days

Febuxostat: Intervention is orally administered to patients in this arm.

Cohort 2

Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg)

Febuxostat: Intervention is orally administered to patients in this arm.

Cohort 3

Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg)

Febuxostat: Intervention is orally administered to patients in this arm.

Cohort 4

Adults

Age, Categorical

Age, Continuous

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Hungary

Italy

Bulgaria

Spain

Weight

Data for all outcome measures were not collected due to the paucity of data in the minor patient population and in agreement with EMA with the exceptions of the secondary outcome Assessment of Treatment Emergent Signs and Symptoms (TESS).

Angela Capriati, MD PhD - Corporate Director Clinical Sciences

Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg)

Febuxostat: Intervention is orally administered to patients in this arm.

Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)

PK Parameter: Apparent Volume of Distribution (Vd/F)

PK Parameter: Absorption Rate Constant (Ka)

PK Parameter: Area Under Curve (AUC)

PK Parameter: Maximum Plasma Concentration (Cmax)

PK Parameter: Tmax

Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)

Assessment of Laboratory Tumor Lysis Syndrome (LTLS)

Assessment of Clinical Tumor Lysis Syndrome (CTLS)

TESS

TESS grade >/=3

Serious TESS

Related TESS

Related TESS grade >/=3

Related TESS/Drug Withdrawn

Assessment of Treatment Emergent Signs and Symptoms (TESS)

Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)

Performance Status (PS) Evaluation

Baseline Period

Treatment Period

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Sarcoma

Liposarcoma

Tertiary Lymphoid Structures

Ichthyosis, X-Linked

Soft Tissue Sarcoma

Antineoplastic Agents

Pembrolizumab

Immunomodulating Agents

Olaparib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Before surgery: Pembrolizumab 200 mg two intravenous (IV) infusions q3w (2 injections: at C1D1 and C1D21)

Before surgery: Pembrolizumab 200 mg two IV infusions q3w (2 injections: at C1D1 and C1D21) + concomitant full dose olaparib (300 mg per os b.i.d) during four weeks

Pembrolizumab and Olaparib

After surgery (adjuvant phase), all patients (Arm A and B) will receive pembrolizumab 200 mg two intravenous (IV) infusions q3w for one-year

Pembrolizumab adjuvant

Sophie Postel-Vinay, MD.

Soft tissue sarcomas represent a subtype of cancer that is both rare and very heterogeneous. When they are organized, their current treatment is essentially based on tumor resection surgery, +/- associated with treatment by chemotherapy and/or radiotherapy. The aim of this treatment is to reduce the risk of local recurrence (appearance of a tumor in the same region where it was first detected) and/or distant (appearance of a tumor in other regions, organs where it was first detected).

Currently, no immunotherapy treatment has been approved for the treatment of patients with sarcoma.

This research is based on the hypothesis that soft tissue sarcomas in which "tertiary lymphoid structures" or "TLS" are found, recognizable by a cluster of specific immune cells within the tumor, would be likely to respond better to the immunotherapy. Furthermore, the combination of immunotherapy and certain drugs targeting DNA repair has demonstrated some effectiveness in other types of cancers.

The research will therefore focus on two experimental drugs :

* Pembrolizumab (immunotherapy) and
* Olaparib (DNA repair inhibitor).

This research will make it possible to evaluate the effectiveness and safety of use of the two drugs.

This study will allow:

* To evaluate the ability of pembrolizumab (with or without olaparib) before surgery to trigger an immune reaction in order to kill tumor cells.
* To evaluate the feasibility of therapy with pembrolizumab for 1 year (with or without radiotherapy) after surgery.

The research is divided into two groups of patients, called "cohorts" depending on the type of soft tissue sarcoma you have:

* Cohort 1: Undifferentiated pleomorphic sarcoma
* Cohort 2: Dedifferentiated liposarcoma

Before surgery, a group of patients will receive pembrolizumab combined with olaparib, a second group will receive only pembrolizumab. All patients will receive pembrolizumab after surgery (for up to 1 year).

Study Evaluating Pembrolizumab +/- Olaparib in TLS Positive Selected Resectable STS Followed by Adjuvant Pembrolizumab

A Window of Opportunity (WoO) Study Evaluating Pembrolizumab With or Without Olaparib in Tertiary Lymphoid Structures (TLS)-Positive Selected Resectable Soft Tissue Sarcoma (STS) Followed by Adjuvant Pembrolizumab

50% increase in CD8+ T-cell tumor infiltration density between baseline biopsy and resection surgery specimen as defined by expert pathologist who will be blinded for treatment arm and patient outcome

Proportion of patients with 70% pathological response on the resection surgery specimen as assessed by expert pathologist after WoO treatment

Quality of resection is defined at time of resection surgery as follows, as initially defined by Hemanek and Wittekind according to both clinical and pathological findings: R0 corresponds to resection for cure or complete remission. R1 to microscopic residual tumor, R2 to macroscopic residual tumor.

Objective Response Rate (ORR) at 4 weeks of WoO treatment defined as the rate of patients with Complete Response (CR) or Partial Response (PR) according to RECIST v1.1

Local Recurrence Rate (LRR) at 2-year post-surgery

Disease Free Survival (DFS) at 2-year post-surgery

Disease Control Rate (DCR) at 4 weeks of WoO according to RECIST v1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rasburicase in Patients at Risk for Tumor Lysis Syndrome	NCT00628628	Tumor Lysis Syn...	As Needed Rasbu... Fixed Dose Rasb...	-	M.D. Anderson Cancer Center
Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS	NCT00360438	Leukemia Lymphoma Tumor Lysis Syn...	Rasburicase	18 Years -	M.D. Anderson Cancer Center
Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS	NCT00360438	Leukemia Lymphoma Tumor Lysis Syn...	Rasburicase	18 Years -	M.D. Anderson Cancer Center
Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults	NCT03605212	Tumor Lysis Syn...	Febuxostat	6 Years -	Menarini Group
Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS	NCT00360438	Leukemia Lymphoma Tumor Lysis Syn...	Rasburicase	18 Years -	M.D. Anderson Cancer Center
Study Evaluating Pembrolizumab +/- Olaparib in TLS Positive Selected Resectable STS Followed by Adjuvant Pembrolizumab	NCT06116578	Cancer	Pembrolizumab Pembrolizumab a... Pembrolizumab a...	18 Years -	Gustave Roussy, Cancer Campus, Grand Paris

Spots Global Cancer Trial Database for tls

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

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