Description:
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.
Title
- Brief Title: Sunitinib in Sarcomas of the Central Nervous System
- Official Title: Phase II Clinical Trial of Sunitinib in Sarcomas of the Central Nervous System
Clinical Trial IDs
- ORG STUDY ID:
180137
- SECONDARY ID:
18-C-0137
- NCT ID:
NCT03641326
Conditions
- Gliosarcoma
- Central Nervous System Sarcoma
Interventions
Drug | Synonyms | Arms |
---|
Sunitinib | | 1 |
Purpose
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.
Detailed Description
Background:
- Gliosarcoma and primary 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 CTCAE version 5.0.
Trial Arms
Name | Type | Description | Interventions |
---|
1 | Experimental | Sunitinib will be administered at a dose of 50 mg daily for 2 consecutive weeks followed by 1 week of rest.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 | |
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have histologically confirmed gliosarcoma (primary or secondary) or
primary central nervous system sarcoma confirmed by the Laboratory of Pathology, NCI.
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured bidimensionally by MRI (or CT scan if MRI is contraindicated).
- Patients must have failed standard therapy consisting of surgery, irradiation, and
chemotherapy if indicated.
- Age greater than or equal to 18 years.
- Karnofsky greater than or equal to 60%.
- Patients must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of
normal
- creatinine within normal institutional limits OR creatinine clearance greater
than or equal to 60 mL/min/1.73 m(2) for patients with
creatinine levels above institutional normal.
- Patients must have the ability to understand and the willingness to sign a written
informed consent document indicating that they are aware of the investigational nature
of this study.
- The effects of sunitinib on the developing human fetus are unknown. For this reason
and because anti-angiogenic agents are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately.
- Tumor tissue blocks or at least 10-15 unstained slides from the diagnosis should be
available.
- At the time of registration, all subjects must be removed greater than or equal to 28
days from any investigational agents.
EXCLUSION CRITERIA:
- Patients who are receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
- Prior use of tyrosine kinase inhibitors or VEGF inhibition.
- Patients who are receiving strong CYP450 inducers or inhibitors are ineligible.
- Pregnant women are excluded from this study because sunitinib has potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
sunitinib, breastfeeding should be discontinued if the mother is treated with
sunitinib.
- Patients with known HIV history on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with sunitinib. In addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy.
- Uncontrolled hypertension (> 150/100 mmHg) while on antihypertensive medications.
- New York Heart Association class II or greater congestive heart failure.
- Serious cardiac arrhythmia requiring medication.
- Baseline echocardiogram with ejection fraction < 50% or greater than or equal to 20%
decrease from a prior study.
- QTc interval > 500 msec on baseline EKG
- Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
such as warfarin are excluded, although doses of up to 2 mg daily are permitted for
prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided
the patient s INR is less than or equal to 1.5.
- Previous exposure to anthracyclines.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | objective response rate (ORR) |
Time Frame: | Enrollment of 16, 24, and 32 study subjects |
Safety Issue: | |
Description: | To determine anti-tumor effect of sunitinib in recurrent gliosarcomas and primary CNS sarcomas as assessed by objective response rate (ORR) |
Secondary Outcome Measures
Measure: | Proportion of patients that have progressive disease after 18 months and median amount of time subject survives after therapy |
Time Frame: | 6 month and death |
Safety Issue: | |
Description: | To determine the 6-month and median progression-free survival rates. |
Measure: | adverse event frequency |
Time Frame: | end of study |
Safety Issue: | |
Description: | To determine the adverse event rate of sunitinib in patients with recurrent gliosarcoma and primary CNS sarcoma. |
Measure: | Evaluation of Tumor Tissue for Biomarkers |
Time Frame: | end of study |
Safety Issue: | |
Description: | To evaluate archival tumor tissue for activation of signaling pathways targeted by sunitinib to establish potential biomarkers of response. |
Measure: | Molecular Profiling of Tumor Tissue |
Time Frame: | end of study |
Safety Issue: | |
Description: | To perform broad unbiased molecular profiling of archival tumor tissues to identify potential novel biomarkers of response to sunitinib. |
Measure: | proportion of patients who |
Time Frame: | end of study |
Safety Issue: | |
Description: | To evaluate radiological parameters such as perfusion and dynamic contrast enhanced MRI before and during treatment with sunitinib. |
Measure: | Proportion of patients that have improvement in quality of life |
Time Frame: | at defined study timepoints and end of study |
Safety Issue: | |
Description: | To longitudinally evaluate patient reported outcome measures using self-reported symptom severity and interference with daily activities using the MDASI-BT |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | National Cancer Institute (NCI) |
Trial Keywords
- Gliosarcoma
- Brain Tumor
- MDASI
Last Updated
May 10, 2021