Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Neoplasm Metastasis

Central Nervous System Diseases

Brain Neoplasms

Breast Diseases

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Antineoplastic Agents

All Drugs and Chemicals

Epothilones

Sagopilone

Tubulin Modulators

Antimitotic Agents

Given intravenously over approximately 30 minutes once every 3 weeks

ZK219477

Nancy Lin, MD

The purpose of this research study is to determine the effects (good and bad) of ZK219477(sagopilone) on participants and their cancer. ZK219477 is a chemotherapy drug that is thought to work by interfering with the ability of cancer cells to grow and divide. It is a part of a group of drugs called "epothilones" which appear to cause shrinkage of cancer in some patients with breast cancer. It is generally difficult for chemotherapy to enter the brain. However, it is believed that ZK219477 crosses into the brain. We are also studying whether an investigational MRI scan procedure may eventually help to predict which patients will benefit from ZK219477.

* Participants will be given ZK219477 intravenously over approximately 30 minutes every three weeks.
* During all treatment cycles a physical exam and questions about the participants general health and specific questions about any problems they may be having will be performed.
* At least every three weeks blood tests will be done to assess the effect of ZK219477 on the body.
* After every 2 cycles of treatment, participants will have additional scans to assess the effect of ZK219477 on their cancer. This will include a CT scan of the abdomen, chest, and pelvis, and an MRI of the brain.
* At the time of the standard MRI, participants will be asked to undergo an additional MRI sequence, which means they will be in the MRI machine for approximately 15-20 more minutes.

ZK219477 (Sagopilone) in Patients With Breast Cancer and Brain Metastases

A Phase 2 Study of ZK219477 (ZK-EPO) in Patients With Breast Cancer and Brain Metastases

Objective response rate is defined as at least a 50 percent reduction in the Central Nervous system target lesion volume compared to the lesion volume at baseline.

Non-CNS response rate (according to RECIST 1.0) limited to patients with measurable non-CNS disease

Time from date of registration until the date of the first documentation of progression or date of death (from any cause),whichever came first, up to 2 years from registration. Progression is defined as either progression in the Central Nervous system (CNS) according to volumetric measurement (Freedman et al. 2011) and /or progression in non-Central Nervous System lesion Measured by RECIST 1.0

CBR = CR + PR + SD \> 24 weeks in CNS with at least stable non-CNS disease

Brigham and Women's Hospital

Bayer

Breast Cancer Research Foundation

Assistant Professor of Medicine

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Nancy Lin

The study was closed prior to full accrual as detailed in the manuscript

Objective Response Rate in the Central Nervous System (CNS)

Study was closed prior to full accrual for reasons detailed in published manuscript

Number of Subjects With Adverse Events (Any Grade)

only included the 8 pts with measurable non-CNS disease at baseline. The 7 pts with non-measurable non-CNS disease at baseline were not included in the denominator for this endpoint

Objective Response Rate in Non-Central Nervous System (CNS) Sites

all patients who received at least 1 dose of protocol therapy

Time to Progression at Any Site.

all pts who received at least 1 dose of protocol therapy

Clinical Benefit Rate.

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Anti-Infective Agents

Cytarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

given intrathecally in induction phase every 15 days until CSF response for up to 7 injections. Then it is given every 4 weeks during consolidation phase while patient awaiting bone marrow transplant. For those patients who are not candidates for a bone marrow transplant, the drug will be given every 3 months for 4 administrations (maintenance therapy)

liposomal cytarabine

Rosanna Parasole, M.D.

Massimo Di Maio, M.D.

Francesco Perrone, M.D., Ph.D.

A. Pession

William Morello

E. Strocchi

The purpose of this study is to describe the activity and toxicity of a new formulation of cytarabine called liposomal cytarabine given into the central nervous system for the treatment of central nervous system localization of acute lymphoblastic leukemia (ALL) in children and adolescents.

Liposomal cytarabine (DepoCyte) is a new formulation of the drug cytarabine, a drug commonly used in the treatment of ALL. This formulation of the drug can be given intrathecally (into the spinal fluid), and is released slowly over a longer period, about two weeks. This allows a longer exposure of the drug to the central nervous system, and requires fewer intrathecal injections for the patient.

Liposomal Cytarabine in the Treatment of Central Nervous System Resistant or Relapsed Acute Lymphoblastic Leukemia in Children

Multicentered Phase II Study Evaluating the Activity and Toxicity of Liposomal Cytarabine in the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia With Resistent or Relapsed Central Nervous System Involvement

date of reaching CSF response is the first date of two consecutive negative cytomorphologic exams of CSF

duration of response is the length of time in days from the date of the CSF response to the date of the first positive cytomorphologic CSF exam

Santobono-Pausilpon Hospital

IRCCS Azienda Ospedaliero-Universitaria di Bologna

University of Bologna

National Cancer Institute, Naples

Pembrolizumab

Trastuzumab

Tucatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.

Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.

Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.

Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.

Reva Basho, MD

This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.

TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases

TOPAZ: Single Arm, Open Label Phase 1b/2 Study of Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases

Percentage of patients who experience objective tumor response \[ partial response (PR) or complete response (CR) \] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.

Proportion of participants with confirmed CR or PR per RANO-BM Criteria

Proportion of participants with confirmed CR or PR per RECIST v.1.1

From date of registration to date of first documentation of true progression or symptomatic deterioration (as defined above), or death due to any cause. Patients last known to be alive and progression free are censored at date of last assessment. PFS will be assessed in the CNS and systemically.

From date of registration to date of death due to any cause. Patient's last known to be alive are censored at date of last contact.

Number of adverse events as assessed per CTCAE v.5.

Merck Sharp & Dohme LLC

Seagen Inc.

Reva Basho

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Amino Acids

Temozolomide

Dasatinib

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Tyrosine

Dasatinib (Sprycel) with Radiotherapy (RT) and 6 weeks of concomitant Temozolomide (TMZ)

Starting dose of 150 mg/day administered by mouth daily on Days 1 to 28 of every 28 day cycle, beginning on the first day of RT.

As a part of standard of care, receive 60 Gy radiation therapy Monday-Friday for a total of 30 radiation treatments (about 6 weeks).

RT (Radiotherapy)

75 mg/m\^2 capsules daily by mouth for up to a maximum of 7 weeks beginning first day of RT until RT end followed by 4 weeks off then 150 mg/m\^2 daily on Days 1-5 of each 28 day study cycle and 200 mg/m\^2 daily of subsequent cycles.

TMZ (Temozolomide)

John De Groot, MD

Phase I:

Primary Objectives:

-To define the maximum tolerated dose (MTD) of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m\^2/day in patients with newly-diagnosed glioblastoma (GBM).

Secondary Objectives:

* To characterize the safety profile of dasatinib (Sprycel) in combination with radiotherapy (RT) and concomitant TMZ in patients with newly-diagnosed GBM.
* To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with glioblastoma after RT.

STUDY DID NOT PROGRESS TO PHASE II PORTION.

Phase II:

Primary Objectives:

-To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m\^2/day followed by adjuvant temozolomide with concurrent dasatinib in patients with newly-diagnosed glioblastoma (GBM) as measured by overall survival.

Secondary Objectives:

* To determine the efficacy of this treatment as measured by radiographic response (RR), progression-free survival (PFS) and time to progression (TTP).
* To characterize the safety profile of dasatinib (Sprycel) in combination with RT and concomitant TMZ in patients with newly-diagnosed GBM.
* To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with GBM after RT.

Exploratory Objectives:

-To correlate tumor genotype, tumor expression of dasatinib target proteins (e.g. Src, EphA2, c-kit and PDGFR), and PTEN levels with response to therapy with dasatinib and temozolomide.

PHASE I

The Study Drugs:

Dasatinib is designed to change the function of certain genes. By changing the function of these genes, it may prevent cancer from growing and spreading. It is also designed to block or lower the activity of one or more tumor-causing proteins responsible for the uncontrolled growth of tumor cells, which may result in shrinking or stopping tumor growth.

Temozolomide is designed to kill cancer cells by damaging DNA (the genetic material of cells). The damaged DNA may cause tumor cell death.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of dasatinib based on when you joined this study. Up to 2 dose levels of dasatinib will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of dasatinib given in combination with temozolomide is found.

All the groups will take the same dose level of temozolomide for the entire study.

The amount of study drugs you receive may change if you experience side effects. If at any time you experience any intolerable side effects, tell the study doctor right away.

Study Drug Administration:

During Radiation:

As a part of standard of care, you will receive radiation therapy Monday-Friday for a total of 30 radiation treatments (about 6 weeks).

Every day while you are receiving radiation, you will take the temozolomide by mouth once a day for up to a maximum of 7 weeks.

You should swallow temozolomide whole, one right after the other, without chewing them. If you vomit while taking temozolomide, you cannot take more capsules before the next scheduled dose. They should be taken on an empty stomach (at least 1 hour before and 2 hours after eating) with 1 cup (about 8 oz.) of water.

Every day while you are receiving radiation, you will take dasatinib by mouth 1 time a day for up to a maximum of 7 weeks. You should take dasatinib without food (1 hour before or 2 hours after eating), with at least 1 cup (8 oz.) of water.

After Radiation:

After the radiation therapy ends, every day, you will continually take dasatinib by mouth 1 time a day.

You will not take temozolomide for about 4 weeks after the radiation therapy ends. After 4 weeks, you will begin taking temozolomide 1 time a day, by mouth, on Days 1-5 of each 28 day study cycle.

Study Visits:

Four (4) weeks after the end of radiation, then every 4 weeks after that, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* You will have a neurological exam.
* You will have a performance status evaluation.
* You will be asked about any drugs you may be taking and if you have experienced any side effects.
* Blood (about 1 teaspoon) will be drawn to check your blood's ability to clot normally.

Every week for the first 6 weeks, then every 4 weeks after that, you will be asked if you have experienced any side effects.

If you are taking an anti-seizure drug, every 2 weeks for the first 6 weeks and then every 4 weeks after that, blood (about 1 teaspoon) will be drawn to check the levels of anti-seizure drug in your blood.

At Week 6, then before each cycle after radiation for the first 6 cycles, you will have an ECG.

Every week for the first 6 weeks, then on Days 1 and 22 of every cycle after radiation, blood (about 3 teaspoons) will be collected for routine tests.

Four (4) weeks after the end of radiation, then every 8 weeks after that, you will have an MRI scan to check the status of the disease.

Length of Study:

You may continue taking temozolomide for up to 12 cycles. You may continue taking dasatinib for as long as you are benefitting. You will be taken off study early if the disease gets worse or you experience intolerable side effects.

End-of-Study Visit:

After you go off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* Your complete medical history will be recorded.
* You will have a physical exam.
* You will have a performance status evaluation.
* You will be asked about any drugs you may be taking and if you have experienced any side effects.
* You will have a neurological exam.
* Blood (about 3 1/2 teaspoons) will be collected for routine tests and to check your blood's ability to clot normally.
* If you are taking an anti-seizure drug, blood (about 1 teaspoon) will be drawn to check the level of anti-seizure drug in your blood.

Long-Term Follow-up visit:

After the end-of-study visit, the study team/staff will contact you by telephone every 3 months to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Temozolomide is FDA approved and commercially available for the treatment of brain tumors. Dasatinib is FDA approved and commercially available for the treatment of some types of leukemia, but it is experimental for use in brain tumors. In addition, the combination of temozolomide and dasatinib is experimental for use in brain tumors. At this time, the combination is only being used in research.

Up to 72 participants will take part in this study. Up to 72 will be enrolled at M. D. Anderson.

Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma

Phase I/II Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma

The MTD of dasatinib will be that dose at which fewer than one-third of participants experience dose limiting toxicity (DLT). Escalations are planned in groups of three patients, with an additional three patients to be added at the first indication of DLT.

Overall survival (OS) is defined as the time from surgical diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ZK219477 (Sagopilone) in Patients With Breast Cancer and Brain Metastases	NCT00496379	Breast Cancer CNS Disease	ZK219477	18 Years -	Dana-Farber Cancer Institute
Liposomal Cytarabine in the Treatment of Central Nervous System Resistant or Relapsed Acute Lymphoblastic Leukemia in Children	NCT01593488	Acute Lymphobla...	liposomal cytar...	18 Years -	National Cancer Institute, Naples
ZK219477 (Sagopilone) in Patients With Breast Cancer and Brain Metastases	NCT00496379	Breast Cancer CNS Disease	ZK219477	18 Years -	Dana-Farber Cancer Institute
TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases	NCT04512261	Breast Cancer Brain Metastase... HER2-positive B... CNS Disease	Tucatinib Pembrolizumab Trastuzumab	18 Years -	Cedars-Sinai Medical Center
Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma	NCT00895960	Glioblastoma CNS Disease Brain Diseases	Dasatinib RT (Radiotherap... TMZ (Temozolomi...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for cns disease

Every month we try and update this database with for cns disease 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 cns disease

Every month we try and update this database with for cns disease 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 cns disease 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.