Sunitinib in Sarcomas of the Central Nervous System

NCT03641326 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 18013718-C-0137
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Gliosarcoma; Central Nervous System Sarcoma

Keywords

Gliosarcoma; Brain Tumor; MDASI

Outcome Measures

Primary Outcomes (1)

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

  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.

  From enrollment to off study, approximately 3 Months, 1 Week, 4 Days

Secondary Outcomes (8)

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

  6 months

• Number of Participants That Have Progressive Disease After 18 Months

  After 18 months

• Number of Adverse Events Related to Drug

  Baseline to off study, approximately 3 months and 12 days

• Evaluation of Tumor Tissue for Biomarkers

  end of study, approximately 25 months and 12 days.

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

  From baseline to end of treatment, approximately 25 months and 12 days.

Other Outcomes (1)

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

  Baseline to off study, approximately 3 months and 12 days

Study Arms (3)

Participants With Primary Gliosarcoma

EXPERIMENTAL

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

Drug: Sunitinib; Device: wGT3x-BT

Participants With Secondary Gliosarcoma

EXPERIMENTAL

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

Drug: Sunitinib; Device: wGT3x-BT

Participants With Primary Central Nervous System (CNS) Sarcoma

EXPERIMENTAL

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

Drug: Sunitinib; Device: wGT3x-BT

Interventions

Sunitinib DRUG

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.

Also known as: Sutent

Participants With Primary Central Nervous System (CNS) Sarcoma; Participants With Primary Gliosarcoma; Participants With Secondary Gliosarcoma

wGT3x-BT DEVICE

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

Also known as: Actigraph

Participants With Primary Central Nervous System (CNS) Sarcoma; Participants With Primary Gliosarcoma; Participants With Secondary Gliosarcoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed gliosarcoma (primary or secondary) or primary central nervous system sarcoma confirmed by the Laboratory of Pathology, National Cancer Institute (NCI).
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured bi-dimensionally by MRI (or computed tomography (CT) scan if magnetic resonance imaging (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
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (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.

You may not qualify if:

• 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 vascular endothelial growth factor (VEGF) inhibition.
• Patients who are receiving strong cytochromes P450 (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 human immunodeficiency virus (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 mm hemoglobin (Hg) 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.
• Corrected QT interval (QTc) \> 500 msec on baseline electrocardiogram (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 international normalized ratio (INR) is less than or equal to 1.5.
• Previous exposure to anthracyclines.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kondo T, Takagi T, Kobayashi H, Iizuka J, Nozaki T, Hashimoto Y, Ikezawa E, Yoshida K, Omae K, Tanabe K. Superior tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-week-off in patients with metastatic renal cell carcinoma--comparison to standard dosing schedule of 4-weeks-on and 2-weeks-off. Jpn J Clin Oncol. 2014 Mar;44(3):270-7. doi: 10.1093/jjco/hyt232. Epub 2014 Jan 27.

  PMID: 24474815 BACKGROUND

• Cachia D, Kamiya-Matsuoka C, Mandel JJ, Olar A, Cykowski MD, Armstrong TS, Fuller GN, Gilbert MR, De Groot JF. Primary and secondary gliosarcomas: clinical, molecular and survival characteristics. J Neurooncol. 2015 Nov;125(2):401-10. doi: 10.1007/s11060-015-1930-y. Epub 2015 Sep 9.

  PMID: 26354773 BACKGROUND

• Finke J, Ko J, Rini B, Rayman P, Ireland J, Cohen P. MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol. 2011 Jul;11(7):856-61. doi: 10.1016/j.intimp.2011.01.030. Epub 2011 Feb 11.

  PMID: 21315783 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Gliosarcoma; Brain Neoplasms

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Mark Gilbert
• Organization: National Cancer Institute

mark.gilbert@nih.gov

240-760-6023

Study Officials

• Mark R Gilbert, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 22, 2018
• Study Start: February 21, 2019
• Primary Completion: April 2, 2021
• Study Completion: April 2, 2021
• Last Updated: April 19, 2022
• Results First Posted: April 19, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)