Sunitinib in Sarcomas of the Central Nervous System
Raktažodžiai
Santrauka
apibūdinimas
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.
Datos
| Paskutinį kartą patikrinta: | 06/22/2020 |
| Pirmasis pateikimas: | 08/20/2018 |
| Numatytas registravimas pateiktas: | 08/20/2018 |
| Pirmas paskelbtas: | 08/21/2018 |
| Paskutinis atnaujinimas pateiktas: | 06/24/2020 |
| Paskutinis atnaujinimas paskelbtas: | 06/25/2020 |
| Faktinė studijų pradžios data: | 02/20/2019 |
| Numatoma pirminio užbaigimo data: | 06/02/2023 |
| Numatoma studijų užbaigimo data: | 09/29/2024 |
Būklė ar liga
Intervencija / gydymas
Drug: 1
Device: 1
Fazė
Rankų grupės
| Ranka | Intervencija / gydymas |
|---|---|
| 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: 1 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. |
Tinkamumo kriterijai
| Amžius, tinkami studijuoti | 18 Years Į 18 Years |
| Tinkamos studijoms lytys | All |
| Priima sveikus savanorius | Taip |
| Kriterijai | - 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. |
Rezultatas
Pirminės rezultatų priemonės
1. objective response rate (ORR) [Enrollment of 16, 24, and 32 study subjects]
Antrinės rezultatų priemonės
1. Proportion of patients that have progressive disease after 18 months and median amount of time subject survives after therapy [6 month and death]
2. adverse event frequency [end of study]
3. Evaluation of Tumor Tissue for Biomarkers [end of study]
4. Molecular Profiling of Tumor Tissue [end of study]
5. proportion of patients who [end of study]
6. Proportion of patients that have improvement in quality of life [at defined study timepoints and end of study]
