Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Sarcoma

Brain Neoplasms

Gliosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Soft Tissue Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Sunitinib will be administered at a dose of 50 mg daily for 2 consecutive weeks followed by 1 week of rest. Participants will be given a small, portable pager-type and watch accelerometers to wear at the hip or non-dominant wrist. Worn daily for 6 cycles

Sunitinib will be administered at a dose of 50 mg daily for 2 consecutive weeks followed by 1 week of rest until there is disease progression or development of intolerable side effects.

Participants will given a small, portable pager-type and watch accelerometers to wear at the hip or non-dominant wrist. Worn daily for 6 cycles

wGT3x-BT

Mark R Gilbert, M.D.

Background:

A sarcoma is a rare cancer. It grows in the body's connective tissue. Sarcomas in the brain and central nervous system are especially rare. The drug Sunitinib has been approved in many countries for treating other types of rare or advanced cancers. These include kidney, pancreas, and bowel cancer. Researchers want to see if it can help people with sarcomas of the central nervous system.

Objective:

To study the effects of Sunitinib on gliosarcomas or sarcomas of the central nervous system.

Eligibility:

Adults ages 18 and older with a gliosarcoma or sarcoma of the central nervous system

Design:

Participants will be screened with the following tests. Some may be done as part of their regular cancer care:

Medical history

Medication review

Physical exam

Blood, heart, and pregnancy tests

Cranial scans to locate and measure their tumor

Participants will take Sunitinib by mouth every day for 2 weeks and then take none of the drug for 1 week. These 3 weeks equal 1 cycle.

Participants will have 2 study visits in cycle 1. They will have 1 visit in all other cycles. They will answer questions about quality of life and repeat some screening tests.

Participants will take their blood pressure at home weekly. They keep a diary of each dose of Sunitinib and blood pressure reading.

Participants can choose to share data about their physical activity levels and quality of sleep. These participants will wear a small, portable watch-sized accelerometer device on the wrist for 6 cycles.

About 1 month after their last study drug dose, participants will have a final study visit. They will have a physical exam, blood tests, and scans.

Background:

* Gliosarcoma and primary central nervous system (CNS) sarcomas are malignant brain tumors uniformly associated with poor outcome.
* There are no known effective medical therapies for these cancers.
* Sunitinib is an orally administered small molecule that inhibits signaling of multiple receptor tyrosine kinases including those known to be activated in CNS sarcomas.

Objectives:

To determine the anti-tumor effect of sunitinib in recurrent gliosarcomas and primary CNS sarcomas as assessed by objective response rate (ORR).

Eligibility:

* Patients with histologically proven gliosarcoma and primary CNS sarcoma at disease relapse after failing standard therapy (surgery and irradiation).
* Tumor tissue blocks or 15 unstained slides should be available
* Subjects must be greater than or equal to 18 years old.
* Karnofsky performance status of greater than or equal to 60
* Patients must have adequate organ function.
* Patients must not have received tyrosine kinase inhibitor(s) in the past.

Design:

* This is a prospective, single institution, single arm, multi-cohort phase II study of sunitinib in subjects with recurrent gliosarcoma and primary CNS sarcoma that have failed prior surgery and irradiation (unless radiation therapy was contraindicated).
* Subjects will be classified into three cohorts: 1) Primary gliosarcoma; 2) Secondary gliosarcoma; 3) Primary CNS sarcoma. Cohort expansion will be carried out at indication of promising response.
* Sunitinib will be administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.
* Toxicity will be assessed every cycle by Common Terminology Criteria in Solid Tumors (CTCAE) version 5.0.

Sunitinib in Sarcomas of the Central Nervous System

Phase II Clinical Trial of Sunitinib in Sarcomas of the Central Nervous System

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Objective Response is defined as all participants who had greater than 50% reduction in Complete Response and Partial Response assessed by the Assessment in Neuro-oncology Criteria (RANO criteria). Complete Response is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) or clinical status. Partial Response is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status.

Progression is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. PFS was assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). Progression is ≥25% increase in T1 gadolinium enhancing disease, increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR), presence of new lesions, and decrease in clinical status.

Progressive disease was assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). Progression is ≥25% increase in T1 gadolinium enhancing disease, increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR), presence of new lesions, and decrease in clinical status.

Adverse events was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

To evaluate archival tumor tissue for activation of signaling pathways targeted by sunitinib to establish potential biomarkers of response.

Molecular profiling of archival tumor tissues was used to identify tumor markers of activation of response to sunitinib in responders and non-responders. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Perfusion was quantitated in responders and non-responders comparing pre and post treatment to determine if the treatment regimen altered vasculature and blood flow to the tumor. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \<25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Dynamic contrast enhanced magnetic resonance imaging (MRI) was performed before and during treatment with sunitinib in responders and non-responders. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the Response Assessment in Neuro-oncology Criteria (RANO criteria). CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is \<50% decrease in T1 gadolinium enhancing disease but \< 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Participants reported outcome measures using a self-reported symptom severity and interference with daily activities using the MDASI-BT. The MDASI-BT consists of symptoms rated on an 11-point scale (0 to 10) to indicate the presence and severity of the symptom, with 0 being "not present" and 10 being "as bad as you can imagine." Each symptom is rated at its worst in the last 24 hours. All patients with at least one valid questionnaire will be included in the analyses. This outcome measure was predicated on change. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity and symptom interference measures.

National Cancer Institute (NCI)

Principal Investigator

Sunitinib administered orally using a continuous schedule at 50 mg per day (with dose adjustments allowed for toxicity) for 2 weeks with 1 week off to constitute a 3-week cycle until disease progression or development of intolerable side-effects.

Participants With Primary Gliosarcoma

Participants With Secondary Gliosarcoma

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

National Institutes of Health (NIH) clinical center is a quaternary care facility where we rely heavily on self-referrals and outside physician referrals for accrual. Competing trials at NIH and outside institutions have shifted interest from this study and physicians are not referring patients for this study. Consequently, we have had low accrual.

Dr. Mark Gilbert

Complete Response

Partial Response

Number of Participants With Greater Than 50% Reduction in Objective Response

Number of Participants With 6-month Progression Free Survival (PFS)

This outcome measure was not analyzed because none of the participants reached 6 months progression free survival (PFS), thus we could not assess participants for 18 months PFS.

Number of Participants That Have Progressive Disease After 18 Months

Number of Adverse Events Related to Drug

Analysis not done. There were not enough samples collected to provide results.

Evaluation of Tumor Tissue for Biomarkers

A responder is a participant with a Complete Response (CR) or Partial Response (PR).

Responders With Primary Gliosarcoma

A non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD).

Non-Responders With Primary Gliosarcoma

Responders With Secondary Gliosarcoma

Non-Responders With Secondary Gliosarcoma

0 participants achieved a response in the responders with primary gliosarcoma group and responders with secondary gliosarcoma group.

Number of Responders and Non-responders With Tumor Markers of Activation

This outcome measure was not done because no data was collected because the perfusion blood volume was not measured.

Number of Responders and Non-responders With a Change in Perfusion Blood Volume Before and After Treatment With Sunitinib.

Baseline

During Treatment

Number of Responders and Non-responders With Dynamic Contrast Enhanced Magnetic Resonance Imaging (MRI) Performed Before and During Treatment With Sunitinib.

Baseline mean symptom severity

Baseline mean symptom interference

Mean symptom severity at disease progression

Mean symptom interference at disease progression

Participants With Primary Gliosarcoma and Secondary Gliosarcoma

2 participants only had baseline MDASI, \& 1 participant had baseline\&off treatment MDASI in the secondary glioblastoma group. The number of participants enrolled =5 \& analyses were performed on a subset of collected data. No conclusions should be drawn from the reported data on whether participants had a change in quality of life. Only treatment toxicity evaluation is meaningful \& this will not vary by the histologic subtype of the tumor. Thus, combining the 2 groups is most logical \& expedient.

Mean Symptom Severity and Interference From Baseline Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Skin and Connective Tissue Diseases

Wounds and Injuries

Dermatitis

Central Nervous System Neoplasms

Medulloblastoma

Nervous System Neoplasms

Ependymoma

Radiodermatitis

Pinealoma

Skin Diseases

Radiation Injuries

Brain Diseases

Central Nervous System Diseases

Germ Cells Tumors

Pineoblastoma

Pineocytoma

Beginning first day of CSI proton radiation therapy, caregivers apply StrataXRT gel to half of the patient's forehead and one ear and placebo to the other half of the forehead and the other ear BID until the last day of radiation therapy.

Placebo Administration

Questionnaire Administration

Wound Dressing Material

Susan L McGovern

This phase I trial studies the side effects of a silicone topical wound dressing (StrataXRT) and to see how well it works in preventing radiation dermatitis (skin burns and side effects caused by radiation) in pediatric patients undergoing radiation therapy. StrataXRT may help prevent or decrease severe skin rash, pain, itching, skin peeling, and dry skin in pediatric patients undergoing radiation therapy to the brain or spinal cord.

PRIMARY OBJECTIVES:

I. To estimate the safety (defined using the Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0) of StrataXRT and placebo by assessing gel-associated toxicities among pediatric patients, aged 2-17 undergoing proton cerebrospinal irradiation (CSI) for central nervous system (CNS) tumors.

II. To estimate the efficacy of StrataXRT as a preventative agent for radiation-associated dermatitis among pediatric patients, aged 2-17 undergoing proton CSI for CNS tumors.

SECONDARY OBJECTIVES:

I. To explore the relationship between dosing and the efficacy of StrataXRT. II. To explore the relationship between the use of StrataXRT and parent-reported symptom experience, as measured by the Radiation-Induced Skin Reaction Assessment Scale (RISRAS).

III. To explore compliance with the application of treatment as documented in a study log by participants.

OUTLINE:

Beginning first day of CSI proton radiation therapy, caregivers apply StrataXRT gel to half of the patient's forehead and one ear and placebo to the other half of the forehead and the other ear twice daily (BID) until the last day of radiation therapy.

StrataXRT in Preventing Radiation Dermatitis in Pediatric Patients Undergoing Radiation Therapy to the Brain or Spinal Cord

A Pilot Study of StrataXRT, a Topical Silicone Barrier, to Prevent Auricular Radiation Dermatitis in Pediatric Patients Undergoing Proton Cerebrospinal Radiation Therapy

Graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Safety will be summarized with standard summary statistics by adverse event (AE), grade, relation, etc. using the CTCAE 5.0. All summaries will be calculated for each control and experimental forehead and ears.

To estimate the efficacy of StrataXRT among pediatric patients.

Will be measured by the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). The RISRAS Radiation-Induced Skin Reaction Assessment Scale will be summarized by control and experimental ears at each time point (baseline, 5 weekly treatment visits, and at treatment completion visit \[last day of radiation therapy\]).

As documented in a study log by participants.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sunitinib in Sarcomas of the Central Nervous System	NCT03641326	Gliosarcoma Central Nervous...	Sunitinib wGT3x-BT	18 Years -	National Institutes of Health Clinical Center (CC)
StrataXRT in Preventing Radiation Dermatitis in Pediatric Patients Undergoing Radiation Therapy to the Brain or Spinal Cord	NCT03990597	Central Nervous... Ependymoma Glioma Malignant Intra... Medulloblastoma Pineoblastoma Primary Central...	Placebo Adminis... Questionnaire A... Wound Dressing ...	2 Years - 17 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for central nervous system sarcoma