Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sunitinib in Sarcomas of the Central Nervous System

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03641326
Recruitment Status : Completed
First Posted : August 22, 2018
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Gliosarcoma Central Nervous System Sarcoma Drug: Sunitinib Device: wGT3x-BT Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of Sunitinib in Sarcomas of the Central Nervous System
Actual Study Start Date : February 21, 2019
Actual Primary Completion Date : April 2, 2021
Actual Study Completion Date : April 2, 2021


Arm Intervention/treatment
Experimental: 1
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
Drug: Sunitinib
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.

Device: wGT3x-BT
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




Primary Outcome Measures :
  1. objective response rate (ORR) [ Time Frame: Enrollment of 16, 24, and 32 study subjects ]
    To determine anti-tumor effect of sunitinib in recurrent gliosarcomas and primary CNS sarcomas as assessed by objective response rate (ORR)


Secondary Outcome Measures :
  1. 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 ]
    To determine the 6-month and median progression-free survival rates.

  2. adverse event frequency [ Time Frame: end of study ]
    To determine the adverse event rate of sunitinib in patients with recurrent gliosarcoma and primary CNS sarcoma.

  3. Evaluation of Tumor Tissue for Biomarkers [ Time Frame: end of study ]
    To evaluate archival tumor tissue for activation of signaling pathways targeted by sunitinib to establish potential biomarkers of response.

  4. Molecular Profiling of Tumor Tissue [ Time Frame: end of study ]
    To perform broad unbiased molecular profiling of archival tumor tissues to identify potential novel biomarkers of response to sunitinib.

  5. proportion of patients who [ Time Frame: end of study ]
    To evaluate radiological parameters such as perfusion and dynamic contrast enhanced MRI before and during treatment with sunitinib.

  6. Proportion of patients that have improvement in quality of life [ Time Frame: at defined study timepoints and end of study ]
    To longitudinally evaluate patient reported outcome measures using self-reported symptom severity and interference with daily activities using the MDASI-BT



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03641326


Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Mark R Gilbert, M.D. National Cancer Institute (NCI)
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03641326    
Other Study ID Numbers: 180137
18-C-0137
First Posted: August 22, 2018    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: May 6, 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Gliosarcoma
Brain Tumor
MDASI
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Gliosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action