Vorinostat (SAHA) in Uterine Sarcoma
Cuvinte cheie
Abstract
Descriere
This is an open-label, single arm, proof of concept-study of the HDAC-inhibitor vorinostat in patients with refractory uterine sarcoma that have been pre-tested for an high expression of HDAC. Patients will receive Vorinostat, 400 mg (4 capsules á 100mg of Zolinza) orally once daily for the first 14 days of a 21 day cycle. Treatment will be continued for 4 cycles (treatment period 1). Patients with a response or stable disease after 4 cycles as determined by computed tomography (CT) of target an non target-lesions will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a 9 months period (treatment periods 2 and 3).
Datele
| Ultima verificare: | 06/30/2020 |
| Primul depus: | 03/26/2018 |
| Inscriere estimată trimisă: | 04/15/2018 |
| Prima postare: | 04/25/2018 |
| Ultima actualizare trimisă: | 07/08/2020 |
| Ultima actualizare postată: | 07/26/2020 |
| Data primelor rezultate transmise: | 07/08/2020 |
| Data primelor rezultate QC trimise: | 07/08/2020 |
| Data primelor rezultate postate: | 07/26/2020 |
| Data actuală de începere a studiului: | 12/13/2017 |
| Data estimată de finalizare primară: | 02/03/2019 |
| Data estimată de finalizare a studiului: | 02/03/2019 |
Stare sau boală
Intervenție / tratament
Drug: Vorinostat, Zolinza Oral Capsules
Fază
Grupuri de brațe
| Braţ | Intervenție / tratament |
|---|---|
| Experimental: Vorinostat, Zolinza Oral Capsules Vorinostat Oral Capsules 400mg daily | Drug: Vorinostat, Zolinza Oral Capsules Vorinostat, 400 mg orally once daily for the first 14 days of a 21 day cycle Treatment will be continued for 4 cycles. Patients with a response or stable disease after 4 cycles will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a period of 9 months. |
Criterii de eligibilitate
| Vârste eligibile pentru studiu | 18 Years La 18 Years |
| Sexe eligibile pentru studiu | Female |
| Acceptă voluntari sănătoși | da |
| Criterii | Inclusion Criteria: - Histologically confirmed metastatic uterine sarcoma (endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyosarcoma, adenosarcoma and carcinosarcoma - High HDAC-positivity of the tumor determined by immunohistochemistry - Patients must have received prior systemic antineoplastic therapy - Patient is not amenable for curative therapy - Age >= 18 years - Estimated life expectancy > 3 months - Measurable disease on CT/MRI (at least one measurable lesion >1cm) or chest X-ray (at least one measurable lesion >2cm) - Karnofsky performance status of 60-100 - Adequate hematologic, renal and hepatic function - Subject is able to swallow and retain oral medication and does not have uncontrolled emesis - No fertility preserved - Written informed consent Exclusion Criteria: - Lack of or low expression of HDAC (see 4.1 "Pre-Screening") - Significant cardiac disease - Other invasive malignant tumor diagnosed within the last 5 years (e.g. metastases from breast cancer in the last 3 years) - Significant bowel obstruction - Severe uncontrolled infection - Known HIV-positivity - Symptomatic brain metastasis or leptomeningeal disease - Pre-existing significant liver disease, severe hepatic impairment (Bilirubin no greater than 1.5 times upper limit of normal (ULN) and/or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) greater than 2.5 times ULN) - Known history of allergic reaction to vorinostat or similar medications - Systemic therapy or an investigational agent within 21 days prior to study inclusion - Uncontrolled hypertension (sustained systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg despite optimal medical management) - Major surgery within 3 weeks of enrollment when diagnosed at an early stage - Symptomatic congestive heart failure - Unstable angina pectoris or cardiac arrhythmia - Myocardial infarction within last 6 months - Known active hepatitis B or hepatitis C - Psychiatric illness/social situations that would limit compliance with study requirements- - Prior history of thrombotic or thromboembolic events, unless adequately controlled by anticoagulant therapy |
Rezultat
Măsuri de rezultate primare
1. Progression-free Survival (PFS) [9 months]
Măsuri de rezultate secundare
1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [9 months]
