Activity and tolerability of Pazopanib in advanced and/or metastatic liposarcoma. A phase II clinical trial.

Phase 1

• Conditions: Advanced and/or metastatic liposarcoma; MedDRA version: 17.1Level: PTClassification code 10024629Term: Liposarcoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.1Level: PTClassification code 10024627Term: LiposarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002745-38-DE
• Lead Sponsor: Grupo Español de Investigacion en Sarcomas

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-02-25
• Last Update Posted: 5 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

1.Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
2.Age ? 18 years or legal age of consent if greater than 18 years
3.Histological confirmed diagnosis of high or intermediate grade malignant liposarcoma with metastatic or locally advanced disease. Formaline fixed paraffin embedded tumour block and/or representative H/E (haematoxylin/eosin) slides must be available for central pathologic review.
4.Patient must have documentation of disease progression within 6 months prior to study entry.
5.Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6.Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located outside of a previously irradiated area. If the only measurable lesion is in a previously irradiated area, RECIST progression should be documented after radiotherapy, in the previous 6 months before study entry.
7.The patient should not be considered eligible for surgery or radical radiotherapy. e.g. Patients to whom surgery/radiotherapy can not be performed with a curative intent due to the extension of the disease. In the case of radiotherapy, it may also be limited due to a previous treatment with radiotherapy in the same area.
8.The patient must have either been considered ineligible for systemic chemotherapy or received at least one previous regimen for relapsed, refractory or metastatic disease. A maximum of three previous lines for advanced/metastatic disease are allowed.
9.The patient should be able to swallow and retain study drug
10.Adequate organ system function as defined in Table 1 of protocol.
11.A subject is eligible to enter and participate in this study if she/he is following the contraceptive indication detailed in protocol.
12.LVEF above the lower limit of normal for the institution, based on ECHO or MUGA.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 74
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

Exclusion Criteria

1.Prior history of malignancies other than liposarcoma.
Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
2.History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
3.Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
4.Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.
5.Corrected QT interval (QTc) > 480 msecs
6.History of any one or more of cardiovascular conditions within the past 6 months.
7.Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ?140 mmHg or diastolic blood pressure (DBP) of ? 90mmHg].
8.History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
9.Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
10.Evidence of active bleeding or bleeding diathesis.
11.Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
12.Recent hemoptysis (? ½ teaspoon of red blood within 8 weeks before first dose of study drug).
13.Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject?s safety, provision of informed consent, or compliance to study procedures.
14.Unable or unwilling to discontinue use of prohibited medications listed in section 7.4 of this protocol or at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
15.Treatment with any of the following anti-cancer therapies:
radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of Pazopanib
chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib
16.Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment
17.Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified