Fibrosarcoma, Leiomyosarcoma, Liposarcoma, Malignant Fibrous Histiocytoma
Conditions
Keywords
Sunitinib malate, SUTENT, SU011248, Soft tissue sarcoma, Gastrointestinal stromal tumors (GIST), MFH, Tyrosine kinase inhibitor, Imatinib mesylate, Phase II
Brief summary
This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity. All patients with unresectable or metastatic soft tissue sarcoma (STS): leiomyosarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH) seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.
Detailed description
This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate, an oral multi-kinase inhibitor. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity which in the opinion of the treating physician or the trial Principal Investigator (PI) compromises the ability of the patient to receive treatment or the patient desires to stop treatment. All patients with unresectable or metastatic STS: leiomyosarcoma, liposarcoma, fibrosarcoma, and MFH seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study. An office visit will be required before the beginning of every cycle every 6 weeks to assess toxicity and for physical examination. Complete blood count (CBC) and differential, comprehensive metabolic panel, and electrocardiogram (ECG) will be obtained at every scheduled visit.
Interventions
For each 6 week cycle, patients will take SU011248 every day in the morning for 4 weeks followed by a 2 week rest period.
Sponsors
Pfizer
H. Lee Moffitt Cancer Center and Research Institute
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
* Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 grade less than or equal to 1. * Adequate organ function as defined by the following criteria: * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less than or equal to 2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy * Total serum bilirubin less than or equal to 1.5 x ULN * Absolute neutrophil count (ANC) greater than or equal to1500/microL * Platelets greater than or equal to 100,000/microL * Hemoglobin greater than or equal to 9.0 g/dL * Serum calcium less than or equal to 12.0 mg/dL * Serum creatinine less than or equal to 1.5 x ULN * Histologically-proven liposarcoma, leiomyosarcoma, fibrosarcoma, or MFH * Measurable disease radiographically * Disease that is deemed surgically unresectable and/or metastatic * Age greater than or equal to 18 years * Life expectancy greater than 16 weeks * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 * Patients may have had up to 3 prior chemotherapies within 4 weeks of starting the study treatment.
Exclusion criteria
* Major surgery or radiation therapy or chemotherapy within 4 weeks of starting the study treatment. * NCI CTCAE version 3 grade 3 hemorrhage within 4 weeks of starting the study treatment. * History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease. * Any of the following within the 6 months prior to study drug administration: * myocardial infarction, * severe/unstable angina, * coronary/peripheral artery bypass graft, * symptomatic congestive heart failure, * cerebrovascular accident or transient ischemic attack, or pulmonary embolism * Ongoing cardiac dysrhythmias of NCI CTCAE greater than or equal to grade 2 * Prolonged QTc interval on baseline electrocardiogram (ECG) \> 500 msec. * Hypertension that cannot be controlled by medications (\>150/100 mm Hg despite optimal medical therapy) * Prior tyrosine kinase inhibitor therapy * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection * Concurrent treatment on another clinical trial, except supportive care or non-treatment trials * Concomitant use of agents known to induce or inhibit CYP3A4 * Concomitant use of agents metabolized by the cytochrome P450 system * Ongoing treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg by mouth \[PO\] daily for thrombo-prophylaxis is allowed) * Pregnancy or breastfeeding patients * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response (OR) | From On Treatment to Off Study - average of 6 months | Objective Radiographic Response Rate. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants' Progression Free Survival (PFS) | From On Treatment to Off Study - average of 6 months | Time to tumor progression defined as the duration of time from start of treatment to time of progression. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST). |
| Participants' Overall Survival (OS) | From On Treatment to Off Study - average of 6 months | The median OS times (months) for liposarcoma, leiomyosarcoma and MFH. |
| Number of Participants With Serious Adverse Events (SAEs) | 4 years, 7 months | Determine the number of participants who experience Serious Adverse events while on sunitinib malate study. |
Countries
United States
Participant flow
Recruitment details
From September 2006 to August 2007, a total of 48 patients were enrolled on the study by the Moffitt Cancer Center Sarcoma Program. In general, the patients had been heavily pretreated previously, with a significant number receiving more than one prior chemotherapy regimen and most with multiple metastatic sites.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Sunitinib Malate (SU011248) Treatment Sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Experimental: Sunitinib Malate (SU011248) Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Region of Enrollment United States | 48 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 48 |
| serious Total, serious adverse events | 13 / 48 |
Outcome results
Primary
Number of Participants With Overall Response (OR)
Objective Radiographic Response Rate. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: From On Treatment to Off Study - average of 6 months
Population: All participants assessable for response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Sunitinib Malate (SU011248) Treatment | Number of Participants With Overall Response (OR) | 1 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Determine the number of participants who experience Serious Adverse events while on sunitinib malate study.
Time frame: 4 years, 7 months
Population: All Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Sunitinib Malate (SU011248) Treatment | Number of Participants With Serious Adverse Events (SAEs) | 13 participants |
Secondary
Participants' Overall Survival (OS)
The median OS times (months) for liposarcoma, leiomyosarcoma and MFH.
Time frame: From On Treatment to Off Study - average of 6 months
Population: All participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Sunitinib Malate (SU011248) Treatment | Participants' Overall Survival (OS) | 18.6 months |
| Leiomyosarcoma Cohort Only | Participants' Overall Survival (OS) | 10.1 months |
| Malignant Fibrous Histiocytoma (MFH) Cohort Only | Participants' Overall Survival (OS) | 13.6 months |
Secondary
Participants' Progression Free Survival (PFS)
Time to tumor progression defined as the duration of time from start of treatment to time of progression. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: From On Treatment to Off Study - average of 6 months
Population: All participants who completed the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Sunitinib Malate (SU011248) Treatment | Participants' Progression Free Survival (PFS) | 3.9 months |
| Leiomyosarcoma Cohort Only | Participants' Progression Free Survival (PFS) | 4.2 months |
| Malignant Fibrous Histiocytoma (MFH) Cohort Only | Participants' Progression Free Survival (PFS) | 2.5 months |