Conditions: Ovarian Cancer
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 30
Healthy volunteers: no

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.

Arms:
arm 1: Topotecan 3.5 mg/m\^2 + Sorafenib dose escalation: arm 2: Topotecan 3.5 mg/m\^2 + Sorafenib 400 mg po daily.

Interventions: intervention 1: Sorafenib intervention 2: Topotecan
Intervention descriptions: intervention 1: Phase I: Dose Escalation, Phase II: MTD

Dose level -1: 200mg po daily Dose level 1: 400mg po daily (MTD) Dose level 2: 400mg po bid intervention 2: 3.5mg/m2 weekly, 3 weeks on and one week off.

Protocol document: