Clinical trial NCT00526799: Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer
Official title: A Phase I/II Study of Sorafenib in Combination With Topotecan for the Treatment of Platinum-Resistant Recurrent Ovarian Cancer or Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN06-111
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Bayer
name: Hoosier Cancer Research Network
First posted: 2007-09-10
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multi-institutional phase I/II clinical trial will test the tolerability and efficacy of the combination sorafenib and topotecan in patients with recurrent ovarian cancer, which is platinum-resistant (recurrence within 6 months from completing platinum based therapy) or refractory (progressive disease during platinum based therapy).

Detailed description: OUTLINE: This is a multi-center study.

* Topotecan: 4mg/m2 weekly, 3 weeks on and one week off.
* Sorafenib: Assigned cohort dose for phase I (up to 12 patients) Maximum tolerated dose for phase II (21 total patients)

Cycles will consist of 4 weeks (28 days) with disease evaluations every 8 weeks.

Non-PD and acceptable toxicity: Patients will continue protocol therapy PD or unacceptable toxicity: Patients will discontinue protocol therapy

ECOG performance status 0-1

Life expectancy: Three (3) months

Hematopoietic:

* White blood cell count (WBC) \> 3 K/mm3
* Hemoglobin (Hgb) \> 9 g/dL
* Platelets \> 100 K/mm3
* Absolute neutrophil count (ANC) \> 1.5 K/mm3
* INR \< 1.5 or a PTT within normal limits. NOTE: Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate.
* No evidence or history of bleeding diathesis or coagulopathy.

Hepatic:

* Bilirubin \< 1.5 x ULN
* Aspartate aminotransferase (AST, SGOT) \< 2.5 x ULN
* Alanine aminotransferase (ALT, SGPT) \< 2.5 x ULN
* Alkaline phosphate \< 2.5 x ULN

Renal:

* Creatinine \< 1.5 x ULN

Cardiovascular:

* No history of myocardial infarction or angina pectoris or angina equivalent within 6 months prior to registration for protocol therapy (the patient may not be on anti-anginal or anti-arrhythmic medications), or have uncontrolled hypertension or congestive heart failure \> class II NYHA

Pulmonary:

* No thrombolic or embolic events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months.
* No pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 28 days prior to registration for protocol therapy.
* No non-pulmonary hemorrhage/bleeding event \> CTCAE Grade 3 within 28 days prior to registration for protocol therapy.

Eligibility criteria: Inclusion Criteria:

* Have histologically-confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer. Enrollment of patients with clear cell histology is encouraged.
* Have measurable disease according to RECIST or detectable disease by 1) CA-125 at least twice the ULN within 14 days prior to registration for protocol therapy; 2) Ascites and/or pleural effusion attributed to tumor; 3) solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST definitions for target lesions.
* Have failed at least one prior platinum based chemotherapeutic regimen.
* No more than 3 prior treatment regimens for epithelial ovarian cancer.
* Prior radiation therapy is allowed to \< 25% of the bone marrow.
* Be at least 4 weeks since last anti-cancer treatment, radiation or surgery at the time of registration for protocol therapy.
* No active cancer in addition to the epithelial ovarian cancer within the last 5 years, with the exception of: superficial skin cancer (basal cell or squamous cell skin carcinoma; carcinoma in situ of the cervix; Stage I endometrial cancer with less than 50% invasion of the myometrium, or other adequately treated Stage I or II cancer in complete remission.
* Age \> 18 years at the time of consent
* Written informed consent and HIPAA authorization for release of personal health information.
* Females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation
* Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

Exclusion Criteria:

* No known or suspected allergy to sorafenib or any agent given in the course of this trial.
* No prior treatment with anti-angiogenesis therapy.
* No active CNS metastases.
* No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
* No concurrent combination anti-retroviral therapy for the treatment of immunodeficiency.
* No clinically significant infections requiring antibiotic treatment.
* No evidence of bowel obstruction, malabsorption, or other contraindication to oral medication.
* No serious non-healing wound, ulcer, or bone fracture.
* No major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy.
* No use of St. John's Wort or rifampin (rifampicin) while on protocol therapy.
* No condition that impairs patient's ability to swallow whole pills.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Each participant was treated at their assigned dose level on 28 day cycles until disease progression or unacceptable toxicity. Participants were evaluated for toxicity every two weeks.
measure: Percentage of Participants With Response
timeFrame: Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
measure: Clinical Benefit
timeFrame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
measure: Duration of Stable Disease
timeFrame: From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely
Other outcomes:
Locations:
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Hospital Cynecologic Oncology
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: Brightwaters
country: United States
facility: Schwartz Gynecologic Oncology, PLLC
state: New York
Study officials:
affiliation: Hoosier Oncology Group, Inc.
name: Daniela Matei, M.D.
role: STUDY_CHAIR
References:
citation: Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G. Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial. Cancer. 2008 Aug 15;113(4):723-32. doi: 10.1002/cncr.23605.