Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer, fallopian tube cancer, primary peritoneal cavity cancer, stage I ovarian epithelial cancer, stage II ovarian epithelial cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer
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 ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer in at least the second remission.
Detailed description
OBJECTIVES: Primary * To determine the 12-month progression-free survival (PFS) rate of women with ovarian epithelial, fallopian tube, or peritoneal cancer in second or greater remission treated with oral sorafenib tosylate. Secondary * To determine the safety and tolerability of prolonged treatment with oral sorafenib tosylate in women with a history of recurrent ovarian cancer. * To correlate serum markers of angiogenesis (i.e., VEGF and bFGF) and tumor markers pAKT, HIF-1 α , and VEGF with 12-month PFS. OUTLINE: Patients receive oral sorafenib twice a day on days 1-28. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection at baseline, every 12 weeks during study, and after completion of study therapy for pharmacokinetic studies. Samples are analyzed for soluble markers of angiogenesis (i.e., VEGF and bFGF) via ELISA and HIF-1 α, VEGF, and pAKT via IHC staining. After completion of study treatment, patients are followed at 4 weeks.
Interventions
DRUGsorafenib tosylate
OTHERimmunoenzyme technique
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
OTHERpharmacological study
Sponsors
National Cancer Institute (NCI)
Bayer
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum * Any stage and grade at diagnosis * Must have received initial cytoreductive surgery and chemotherapy with ≥ 1 platinum-based chemotherapy regimen * Persistent or recurrent disease after initial therapy * In complete clinical remission after chemotherapy for recurrent disease, meeting all of the following criteria: * CA125 ≤ 35 units/L * Normal physical examination * No definite evidence of disease by CT scan of the abdomen and pelvis * Lymph nodes and/or soft tissue abnormalities ≤ 1.0 cm are not considered definite evidence of disease * No known brain metastases PATIENT CHARACTERISTICS: Inclusion criteria: * Karnofsky performance status 70-100% * Life expectancy \> 3 months * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9.0 g/dL * INR \< 1.5 OR PT/PTT within normal limits * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Urinalysis negative for protein * If urinalysis shows 1+ protein by dipstick or protein ≥ 30-100 mg/dL by semi-quantitative assay, a 24-hour urine collection is required * Eligible patients must have a total urinary protein ≤ 500 mg AND measured creatinine clearance ≥ 50 mL/min from a 24-hour urine collection * Bilirubin ≤ 1.5 times ULN * AST and ALT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Stable blood pressure (BP) measurement required on 3 separate days prior to the start of treatment * No peripheral neuropathy \> grade 1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception
Exclusion criteria
* Other invasive malignancies within the past 5 years, except nonmelanoma skin cancer * Uncontrolled concurrent illness or medical condition including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Uncontrolled diabetes * Psychiatric illness or social situation that would preclude study compliance * Uncontrolled hypertension defined as a persistent BP \> 150/100 mm Hg (or a persistent BP \> 180/90 mm Hg if the patient has a history of isolated systolic hypertension) despite ≥ 2 attempts at antihypertensive medication dosage adjustment ≥ 2 weeks apart * Thrombolic or embolic events such as cerebrovascular accident, including transient ischemic attack, within the past 6 months * Pulmonary hemorrhage or bleeding event ≥ grade 2 within 4 weeks of the first dose of study drug * Other hemorrhage or bleeding event ≥ grade 3 within 4 weeks of the first dose of study drug * Serious nonhealing wound, ulcer, or bone fracture * Evidence or history of bleeding diathesis or coagulopathy * Inability to take oral medications or gastrointestinal condition that compromises absorption * History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate PRIOR CONCURRENT THERAPY: Inclusion criteria: * See Disease Characteristics * No prior sorafenib tosylate or other inhibitors of MAPK signaling intermediates or angiogenesis inhibitors * No prior cancer treatment that would contraindicate protocol therapy * More than 4 weeks since prior radiotherapy * More than 3 weeks since prior chemotherapy, biological therapy, or immunotherapy * More than 1 week since prior hormonal therapy for cancer treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Rate at 12 Months | 1 year | All 5 patients experienced a rash. As a result, all 5 were either advised to withdraw from the protocol, or withdrew themselves from the protocol. The outcome was not met. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Sorafenib (BAY43-9006) Sorafenib will be administered as 400 mg orally daily x 28 days (continuous). | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Oral Sorafenib (BAY43-9006) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Progression-free Survival (PFS) Rate at 12 Months
All 5 patients experienced a rash. As a result, all 5 were either advised to withdraw from the protocol, or withdrew themselves from the protocol. The outcome was not met.
Time frame: 1 year
Population: Protocol terminated prior to primary outcome evaluation. All 5 patient were evaluable for toxicity only.