Sarcoma
Conditions
Keywords
adult angiosarcoma, adult leiomyosarcoma, adult liposarcoma, adult malignant hemangiopericytoma, recurrent adult soft tissue sarcoma, stage III adult soft tissue sarcoma, stage IV adult soft tissue sarcoma
Brief summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with advanced soft tissue sarcomas.
Detailed description
OBJECTIVES: * Determine the objective response rate (confirmed, complete, and partial) in patients with advanced soft tissue sarcomas treated with sorafenib. * Determine the 4-month progression-free survival rate in patients treated with this drug. * Determine the frequency and severity of adverse events in patients treated with this drug. OTHER OBJECTIVES (if funding permits): * Correlate, preliminarily, a decrease in standard uptake variable (SUV) of target lesions by positron-emission tomography scan at 4 weeks with response in patients treated with this drug. * Correlate, preliminarily, the phosphorylation status of KIT, PDGFR, VEGFR, and the raf/mek/erk pathway with response in patients treated with this drug. * Correlate, preliminarily, the most common B-raf kinase mutation with response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to histology (leiomyosarcoma vs liposarcoma vs angiosarcoma, hemangiosarcoma, or hemangiopericytoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 8 weeks until disease progression and then every 6 months for 2 years and annually for up to 3 years. PROJECTED ACCRUAL: A total of 45-75 patients (15-25 per stratum) will be accrued for this study within 15-38 months.
Interventions
DRUGsorafenib
800 mg per day, daily until progression
Sponsors
National Cancer Institute (NCI)
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
DISEASE CHARACTERISTICS: * Histologically confirmed soft tissue sarcoma of 1 of the following histologies: * Angiosarcoma, cutaneous or visceral * Malignant hemangiosarcoma * Malignant hemangiopericytoma * Grade 3-4 leiomyosarcoma * Grade 3-4 liposarcoma * Must have evidence of unresectable residual disease, metastatic disease, or recurrent disease by radiography * Measurable disease by x-ray, scans, or physical examination * Archived paraffin-embedded tumor sections available * No known brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * WBC ≥ 3,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if due to liver metastases) * Bilirubin normal (≤ 2.5 times ULN if due to liver metastases) * PT, PTT, and INR normal Renal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No history of thromboembolic disease * No uncontrolled hypertension Other * Not pregnant or nursing * Fertile patients must use effective contraception * Able to swallow oral medication * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 28 days since prior chemotherapy (42 days for carmustine or mitomycin) and recovered * Prior adjuvant chemotherapy allowed * No more than 1 prior chemotherapy regimen for metastatic disease Endocrine therapy * Not specified Radiotherapy * At least 28 days since prior radiotherapy and recovered * Must have evidence of disease progression within, or measurable disease outside of, the radiation field after completion of radiotherapy Surgery * At least 28 days since prior major surgery and recovered Other * No prior sorafenib * No prior inhibitor of VEGFR or MAPK pathway * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent therapeutic anticoagulation * No concurrent administration of any of the following medications: * Rifampin * Hypericum perforatum (St. John's wort) * Cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following: * Phenytoin * Carbamazepine * Phenobarbital
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (Confirmed, Complete and Partial) | Assessment performed every eight weeks until progression. | Partial response (PR) is greater than or equal to 30% decrease under baseline of sum of longest diameters of all target measurable lesions; No unequivocal progression of non-measurable disease; No new lesions. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration. Stable disease does not qualify for CR, PR, Progression or Symptomatic Deterioration. Progressive disease is any one or more of the following: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Assessment inadequate is progression or symptomatic deterioration has not been documented, and one or more target measurable lesions have not been assessed or inconsistent assessment methods were used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Four-month Progression-free Survival Rate | 0 - 4 months | — |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events two weeks after starting protocol treatment and then after every cycle of treatment (1 cycle = 28 days) for the duration of protocol treatment. | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 - Severe, Grade 4 - Life-threatening, Grade 5 - Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (BAY 43-9006) Sorafenib (BAY 43-9006) 800 mg per day divided into two equal doses of 400 mg by mouth (PO). Patients received the drug continuously on a daily basis until progression; each cycle is 28 days. All eligible patients who received treatment were included in baseline measures. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Ineligible | 13 |
| Overall Study | Never received treatment | 1 |
| Overall Study | Not Protocol Specified | 4 |
| Overall Study | Progression | 31 |
Baseline characteristics
| Characteristic | Sorafenib (BAY 43-9006) |
|---|---|
| Age, Continuous | 62.7 years |
| Histology Leiomyosarcoma | 19 participants |
| Histology Liposarcoma | 10 participants |
| Histology Soft Tissue Sarcoma of Vascular Derivation | 8 participants |
| Performance Status 0 | 15 participants |
| Performance Status 1 | 22 participants |
| Race/Ethnicity, Customized Black | 3 participants |
| Race/Ethnicity, Customized Pacific Islander | 1 participants |
| Race/Ethnicity, Customized White | 33 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 37 / 37 |
| serious Total, serious adverse events | 10 / 37 |
Outcome results
Primary
Objective Response (Confirmed, Complete and Partial)
Partial response (PR) is greater than or equal to 30% decrease under baseline of sum of longest diameters of all target measurable lesions; No unequivocal progression of non-measurable disease; No new lesions. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration. Stable disease does not qualify for CR, PR, Progression or Symptomatic Deterioration. Progressive disease is any one or more of the following: 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration. Assessment inadequate is progression or symptomatic deterioration has not been documented, and one or more target measurable lesions have not been assessed or inconsistent assessment methods were used.
Time frame: Assessment performed every eight weeks until progression.
Population: Eligible patients who had received any treatment were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leiomyosarcoma | Objective Response (Confirmed, Complete and Partial) | Unconfirmed PR | 1 participants |
| Leiomyosarcoma | Objective Response (Confirmed, Complete and Partial) | Stable disease/no response | 8 participants |
| Leiomyosarcoma | Objective Response (Confirmed, Complete and Partial) | Progressive disease | 9 participants |
| Leiomyosarcoma | Objective Response (Confirmed, Complete and Partial) | Assessment inadequate | 1 participants |
| Liposarcoma | Objective Response (Confirmed, Complete and Partial) | Assessment inadequate | 2 participants |
| Liposarcoma | Objective Response (Confirmed, Complete and Partial) | Unconfirmed PR | 0 participants |
| Liposarcoma | Objective Response (Confirmed, Complete and Partial) | Progressive disease | 6 participants |
| Liposarcoma | Objective Response (Confirmed, Complete and Partial) | Stable disease/no response | 2 participants |
| Vascular Sarcomas | Objective Response (Confirmed, Complete and Partial) | Assessment inadequate | 1 participants |
| Vascular Sarcomas | Objective Response (Confirmed, Complete and Partial) | Stable disease/no response | 5 participants |
| Vascular Sarcomas | Objective Response (Confirmed, Complete and Partial) | Progressive disease | 1 participants |
| Vascular Sarcomas | Objective Response (Confirmed, Complete and Partial) | Unconfirmed PR | 1 participants |
Secondary
Four-month Progression-free Survival Rate
Time frame: 0 - 4 months
Population: Eligible patients who had received any treatment were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leiomyosarcoma | Four-month Progression-free Survival Rate | 42 percentage of participants |
| Liposarcoma | Four-month Progression-free Survival Rate | 30 percentage of participants |
| Vascular Sarcomas | Four-month Progression-free Survival Rate | 63 percentage of participants |
| Total | Four-month Progression-free Survival Rate | 43 percentage of participants |
Secondary
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 - Severe, Grade 4 - Life-threatening, Grade 5 - Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Patients were assessed for adverse events two weeks after starting protocol treatment and then after every cycle of treatment (1 cycle = 28 days) for the duration of protocol treatment.
Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | AST, SGOT | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Alkaline phosphatase | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Amylase | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Constipation | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 4 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 2 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hypertension | 2 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lipase | 6 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Nausea | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pain - Abdomen NOS | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pancreatitis | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 1 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Potassium, serum-low (hypokalemia) | 2 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash/desquamation | 2 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash: hand-foot skin reaction | 4 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 2 Participants |
| Leiomyosarcoma | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Vomiting | 1 Participants |