Sorafenib + Topotecan for Platinum-Resistant Recurrent Ovarian Cancer
Sleutelwoorden
Abstract
Omschrijving
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.
Datums
| Laatst geverifieerd: | 01/31/2016 |
| Eerste ingediend: | 09/04/2007 |
| Geschatte inschrijving ingediend: | 09/04/2007 |
| Eerst geplaatst: | 09/09/2007 |
| Laatste update ingediend: | 02/03/2016 |
| Laatste update geplaatst: | 03/02/2016 |
| Datum van eerste ingediende resultaten: | 12/14/2015 |
| Datum van eerste ingediende QC-resultaten: | 02/03/2016 |
| Datum van eerste geposte resultaten: | 03/02/2016 |
| Werkelijke startdatum van het onderzoek: | 08/31/2007 |
| Geschatte primaire voltooiingsdatum: | 12/31/2009 |
| Geschatte voltooiingsdatum van het onderzoek: | 07/31/2010 |
Conditie of ziekte
Interventie / behandeling
Drug: Sorafenib
Drug: Topotecan
Fase
Armgroepen
| Arm | Interventie / behandeling |
|---|---|
| Experimental: Phase I Topotecan 3.5 mg/m^2 + Sorafenib dose escalation: | |
| Experimental: Phase II Topotecan 3.5 mg/m^2 + Sorafenib 400 mg po daily. |
Geschiktheidscriteria
| Leeftijden die in aanmerking komen voor studie | 18 Years Naar 18 Years |
| Geslachten die in aanmerking komen voor studie | Female |
| Accepteert gezonde vrijwilligers | Ja |
| 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. |
Resultaat
Primaire uitkomstmaten
1. Maximum Tolerated Dose (MTD) [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.]
2. Percentage of Participants With Response [Disease assessments were conducted on the 8th week (Cycle 2, Week 4) and every eight weeks there after, until treatment discontinuation]
Secundaire uitkomstmaten
1. Progression-free Survival [From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely]
2. Clinical Benefit [From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely]
3. Duration of Stable Disease [From enrollment until treatment discontinuation. Participants may remain on study drug indefinitely]
