Liposarcoma, Metastatic Liposarcoma, Surgically Unresectable Liposarcoma
Conditions
Keywords
Liposarcoma
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of single agent pazopanib in subjects with unresectable or metastatic liposarcoma.
Detailed description
This is a Phase II, multicenter, prospective, open label, single arm study. The primary endpoint of the study is progression-free rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 at week 12 after start of treatment. The secondary endpoints include overall progression-free survival (PFS), response rate (RR), duration of response, overall survival (OS), and toxicity assessment through the reporting of adverse events.
Interventions
DRUGpazopanib
Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
Sponsors
Novartis
Vector Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent. * Age \> or = to 18 years. * Histologically or cytologically confirmed high- or intermediate-grade liposarcoma (allowed subtypes include liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, or not otherwise specified). * Surgically unresectable or metastatic disease. * Any number of prior treatment treatment regimens, including treatment naive subjects. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Measurable or evaluable (non-measurable) disease per RECIST guidelines version 1.1. Subjects must have documented disease progression within the past 6 months. * Adequate organ system function determined within 14 days prior to first dose of study treatment. * Left ventricular ejection fraction (LVEF) \> 50% of the institutional LLN within 28 days prior to the first dose of study treatment. * Females must be of either non-child bearing potential or have a negative pregnancy test within 7 days prior to the first dose of study treatment.
Exclusion criteria
* Well differentiated liposarcoma. * Prior treatment with tyrosine kinase inhibitors (TKIs) or vascular endothelial growth factor (VEGF) inhibitors. * Prior malignancy (Note: 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). * History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug * Clinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding. * Clinically significant GI abnormalities that may affect absorption of investigational product. * Presence of uncontrolled infection. * Corrected QT interval \> 480 msecs using Bazett's formula. * History of certain cardiovascular conditions within the past 6 months. * Poorly controlled hypertension \[defined as systolic blood pressure of \> or = 140 mmHg or diastolic blood pressure \> or = 90 mmHg\]. * History of cerebrovascular accident including transient ischemic attack, pulmonary embolism, or untreated deep vein thrombosis within the past 6 months. * Prior major surgery or trauma within 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. * Evidence of active bleeding or bleeding diathesis. * Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. * Hemoptysis in excess of 2.5 mL within 8 weeks of first dose of study drug. * 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. * Unable or unwilling to discontinue use of prohibited medications for 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 study treatment. * Radiation therapy, minor surgery, tumor embolization, 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 study drug. * Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study drug. * Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or that is progressing in severity, except alopecia. * Known immediate or delayed hypersensitivity reaction to idiosyncrasy to drugs chemically realted to pazopanib or excipients that contraindicates participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-week Progression Free Rate | Assessed after 12 weeks of study treatment | Progression will be as defined per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.1. Subjects who remain under observation and progression free at 12 weeks will be defined as treatment successes. Subjects who progress per RECIST by 12 weeks or who drop out without evidence of progression prior to 12 weeks will be defined as treatment failures.Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a \>=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of \>=1 new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Date of Consent until progression or death, up to 27 months | PFS was measured from date of consent until the subject experiences disease progression (assessed approximately every 12 weeks) or death, whichever came first, up to 27 months. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 27 months. |
| Best Overall Response | Date of consent until end of study treatment, up to 32 months | Best overall response is defined as the best response across all time points. Repeat radiologic imaging was conducted after every 3 cycles of treatment (approximately every 12 weeks). Response was evaluated using RECIST v1.1 guidelines, where complete response (CR) is the disappearance of all target and non-target lesions; partial response (PR) is \>=30% decrease in the sum of diameters of target lesions; progressive disease (PD) is \>=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of \>=1 new lesion; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Duration of Response | Measure of the amount of time that the criteria for response per RECIST are first met until disease progression | Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Confirmation of CR or PR is required by repeat scans that should be performed 4 weeks after the criteria for response are first met. |
| Overall Survival (OS) | Date of Consent until death, up to 32 months | OS was measured from date of consent until time of death from any cause, up to 32 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pazopanib Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.
pazopanib: Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ineligible pathology | 1 |
Baseline characteristics
| Characteristic | Pazopanib |
|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 15.52 |
| Gender Female | 14 Participants |
| Gender Male | 27 Participants |
| Region of Enrollment United States | 41 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 41 |
| serious Total, serious adverse events | 17 / 41 |
Outcome results
Primary
12-week Progression Free Rate
Progression will be as defined per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.1. Subjects who remain under observation and progression free at 12 weeks will be defined as treatment successes. Subjects who progress per RECIST by 12 weeks or who drop out without evidence of progression prior to 12 weeks will be defined as treatment failures.Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as a \>=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of \>=1 new lesion.
Time frame: Assessed after 12 weeks of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pazopanib | 12-week Progression Free Rate | 68.29 percentage of participants |
Secondary
Best Overall Response
Best overall response is defined as the best response across all time points. Repeat radiologic imaging was conducted after every 3 cycles of treatment (approximately every 12 weeks). Response was evaluated using RECIST v1.1 guidelines, where complete response (CR) is the disappearance of all target and non-target lesions; partial response (PR) is \>=30% decrease in the sum of diameters of target lesions; progressive disease (PD) is \>=20% increase in the sum of diameters of target lesions, or a measurable increase in a non-target lesion, or the appearance of \>=1 new lesion; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Date of consent until end of study treatment, up to 32 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pazopanib | Best Overall Response | Complete response | 0 percentage of participants |
| Pazopanib | Best Overall Response | Partial Response | 2.4 percentage of participants |
| Pazopanib | Best Overall Response | Inevaluable | 12.2 percentage of participants |
| Pazopanib | Best Overall Response | Stable Disease | 41.5 percentage of participants |
| Pazopanib | Best Overall Response | Progressive Disease | 43.9 percentage of participants |
Secondary
Duration of Response
Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Confirmation of CR or PR is required by repeat scans that should be performed 4 weeks after the criteria for response are first met.
Time frame: Measure of the amount of time that the criteria for response per RECIST are first met until disease progression
Population: Since so few patients experienced a response, the pre-specified endpoint of duration of response was not analyzed.
Secondary
Overall Survival (OS)
OS was measured from date of consent until time of death from any cause, up to 32 months.
Time frame: Date of Consent until death, up to 32 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib | Overall Survival (OS) | 12.62 months |
Secondary
Progression Free Survival (PFS)
PFS was measured from date of consent until the subject experiences disease progression (assessed approximately every 12 weeks) or death, whichever came first, up to 27 months. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 27 months.
Time frame: Date of Consent until progression or death, up to 27 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib | Progression Free Survival (PFS) | 4.44 months |