Chondrosarcoma, Metastatic Chondrosarcoma
Conditions
Keywords
surgically unresectable chondrosarcoma
Brief summary
The purpose of this study is to determine the effectiveness and safety of single agent pazopanib in subjects with chondrosarcoma.
Detailed description
This research study is being conducted in adult subjects with a type of bone cancer called chondrosarcoma that has spread to other parts of the body and is not able to be removed with surgery. There is only one study drug that will be used in this study. It is a drug that interferes with cell communication and growth, taken orally. The study drug is called pazopanib.
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.
Sponsors
GlaxoSmithKline
Emerald Clinical Inc.
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 confirmed diagnosis of conventional chondrosarcoma of any grade. * Surgically unresectable or metastatic disease. * Any number of prior treatment regimens, including treatment naive subjects. Prior treatment with tyrosine kinase inhibitors is permitted. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Measurable or evaluable (non-measurable) disease per RECIST guidelines version 1.1. * Adequate organ system function determined within 14 days prior to first dose of study treatment. * Left ventricular ejection fraction \> 50% or the institutional LLN within 28 days prior to the first dose of study treatment. * Females must either be of non-child bearing potential or have a negative serum pregnancy test within 7 days prior to the first dose of study treatment.
Exclusion criteria
* Prior treatment with pazopanib. * Mesenchymal, dedifferentiated, and extraskeletal myxoid chondrosarcoma subtypes. * 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 (CNS) 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 \[defined as systolic blood pressure of \> or = 140 mmHg or diastolic blood pressure of \> or = 90 mmHg\]. * History of cerebrovascular accident including transient ischemic attack, pulmonary embolism, or untreated deep venous 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, surgery (except major 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. * 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 or idiosyncrasy to drugs chemically related to pazopanib or excipients that contraindicates participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control at Week 16 | Assessed at week 16 of study treatment | Disease control at week 16 defined as complete response (CR), Disappearance of all target lesions; plus partial response (PR), At least a 30% decrease in the sum of diameters of the target lesions taking as reference the Baseline sum diameters; plus stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on the study; where tumor response is defined by RECIST (Response Evaluation Criteria in Solid Tumors) guidelines version 1.1. Repeat radiologic imaging is performed after every 2 cycles of treatment (approximately every 8 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Cycle 1 day 1 until the subject experiences disease progression | The time origin for PFS will be cycle 1 day 1. Repeat radiologic imaging will be conducted after every 2 cycles of treatment (approximately every 8 weeks). No upper limits of duration of assessment are identified or defined in the protocol. |
| Overall Survival (OS) | Cycle 1 day 1 until 6 months after end of treatment, is lost to follow-up, or withdraws consent | The time origin for OS will be cycle 1 day 1. Subjects will be followed until 6 months after end of treatment, lost to follow-up, or withdrawal of consent. No upper limits of duration of assessment are identified or defined in the protocol. |
Countries
United Kingdom, 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.
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. | 47 |
| Total | 47 |
Baseline characteristics
| Characteristic | Pazopanib |
|---|---|
| Age, Continuous | 58 years |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 39 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants |
| Region of Enrollment United Kingdom | 2 participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 47 |
| other Total, other adverse events | 39 / 47 |
| serious Total, serious adverse events | 19 / 47 |
Outcome results
Primary
Disease Control at Week 16
Disease control at week 16 defined as complete response (CR), Disappearance of all target lesions; plus partial response (PR), At least a 30% decrease in the sum of diameters of the target lesions taking as reference the Baseline sum diameters; plus stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum diameters while on the study; where tumor response is defined by RECIST (Response Evaluation Criteria in Solid Tumors) guidelines version 1.1. Repeat radiologic imaging is performed after every 2 cycles of treatment (approximately every 8 weeks).
Time frame: Assessed at week 16 of study treatment
Population: Tumor responses were evaluable in 42 out of 47 patients; 5 patients discontinued prior to the first tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pazopanib | Disease Control at Week 16 | 43 Percentage of CR+PR+SD |
Secondary
Overall Survival (OS)
The time origin for OS will be cycle 1 day 1. Subjects will be followed until 6 months after end of treatment, lost to follow-up, or withdrawal of consent. No upper limits of duration of assessment are identified or defined in the protocol.
Time frame: Cycle 1 day 1 until 6 months after end of treatment, is lost to follow-up, or withdraws consent
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib | Overall Survival (OS) | 17.6 months |
Secondary
Progression Free Survival (PFS)
The time origin for PFS will be cycle 1 day 1. Repeat radiologic imaging will be conducted after every 2 cycles of treatment (approximately every 8 weeks). No upper limits of duration of assessment are identified or defined in the protocol.
Time frame: Cycle 1 day 1 until the subject experiences disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pazopanib | Progression Free Survival (PFS) | 7.9 months |