Clinical trial NCT00522301: Sorafenib in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in at Least the Second Remission
Official title: A Phase II Trial of Oral Sorafenib (Bay43-9006) In Women With Epithelial Ovarian, Fallopian Tube Or Peritoneal Carcinoma In Second Or Greater Remission
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Bayer
First posted: 2007-08-29
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Exclusion criteria:

* Major surgery (i.e., laparotomy) within the past 4 weeks or minor surgery within the past 2 weeks

  * Placement of a vascular access device is not considered minor surgery
* Concurrent combination antiretroviral therapy for HIV-positive patients
* Concurrent St. John wort, rifampin, or enzyme-inducing anticonvulsants (e.g., carbamazepine, phenytoin, or phenobarbital)

Primary outcomes:
measure: Progression-free Survival (PFS) Rate at 12 Months
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan - Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: William P. Tew, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Paul Sabbatini, MD
role: PRINCIPAL_INVESTIGATOR
References: