Gynecologic Tumors Clinical Trial
Official title:
A Phase I Trial of Oral Metronomic Topotecan in Combination With Oral Pazopanib Utilizing a Daily Dosing Schedule to Treat Recurrent or Persistent Gynecologic Tumors
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors.
| Status | Completed |
| Enrollment | 33 |
| Est. completion date | September 2015 |
| Est. primary completion date | June 2015 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Subjects must provide written informed consent prior to the performance of study specific procedures, and must be willing to comply with treatment and follow-up. - Female patients, greater than 18 years of age with a histologically confirmed recurrent/persistent gynecologic malignancy. - For patients with recurrent/persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: persistent disease = progression during primary platinum therapy; recurrent disease = disease that recurs = 12 months after discontinuing primary platinum therapy; if disease recurrence occurs > 12 months after discontinuing primary platinum therapy, there must be progression either during a 2nd platinum therapy or < 6 months after discontinuing the 2nd platinum therapy. - For patients with other gynecologic malignancies: - Malignancy is metastatic or unresectable and no curative or palliative measures exist or are no longer effective. - Maximum of two total prior treatments (this includes neoadjuvant, adjuvant, and metastatic settings) for the recurrent or persistent gynecologic tumors including chemotherapy, hormonal therapy, investigational therapy, radiation therapy, etc.) - Disease may be measurable or non-measurable according to RECIST version 1.0 - Gynecologic Oncology Group (GOG) performance status of 0,1,or 2 - Must have a life expectancy of at least six months - Adequate bone marrow, liver, renal, and cardiac function at study entry as assessed by the following: - Hemoglobin > 9.0 g/dL. - Absolute neutrophil count (ANC) = 1.5 x 10^9/L. - Platelet count = 100 x 10^9/L. - Prothrombin time (PT) or international normalized ratio (INR) < 1.2 x upper limit of normal (ULN). - Partial thromboplastin time (PTT) < 1.2 x ULN. - Total bilirubin = 1.5 x ULN. - Alanine transaminase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN. - Creatinine = 1.5 mg/dL or if serum creatinine is greater than 1.5 mg/dL, calculated creatinine clearance must be > 50 mL/min - Urine dipstick for protein < 2+ or urine protein creatinine (UPC) ratio < 1.0. - Left ventricular ejection fraction (LVEF) = 50% or the institutional lower limit of normal (LLN) - Patients must be physiologically incapable of becoming pregnant, be postmenopausal, or have a negative pregnancy test and agree to use adequate contraception. Exclusion Criteria: - Treatment naive patients. - Repetitive or prolonged neutropenia or thrombocytopenia during previous therapy. - Concurrent malignancy other than malignancies under study. Subjects who have had another malignancy and have been disease free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. - Prior radiation therapy. - Myelosuppressive chemotherapy within the past 28 days or has not recovered from the myelosuppressive effects of recent chemotherapy. - Use of an investigational agent, including an investigational anti-cancer agent, immunotherapy, biological therapy, or hormonal therapy within 28 days prior to the first dose of study treatment. - Prior major surgery or trauma within 28 days prior to the first dose of study treatment and/or presence of any non-healing wound, fracture, or ulcer. - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis. - Inability to swallow a capsule or clinically significant gastrointestinal abnormalities including, but not limited to: - Malabsorption syndrome - Major resection of the stomach or small bowel that could affect the absorption of study treatment - Active peptic ulcer disease - Inflammatory bowel disease - Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment. - Unresolved bowel obstruction or diarrhea = Grade 1 - Known intraluminal metastatic lesion(s) with risk of bleeding - Known endobronchial lesions or involvement of large pulmonary vessels by tumor. - Presence of uncontrolled infection. - Prolongation of corrected QT interval > 480 milliseconds. - History of any one or more of the following cardiovascular conditions within the past 6 months: - Cardiac angioplasty or stenting - Myocardial infarction - Unstable angina - Coronary artery bypass graft - Symptomatic peripheral vascular disease - Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) - Poorly controlled hypertension (defined as systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. - History of cerebrovascular accident, transient ischemic attack, pulmonary embolism, or insufficiently treated deep vein thrombosis (DVT) within the past 6 months. Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible - Evidence of active bleeding or bleeding diathesis. - Recent hemoptysis in excess of 2.5 mL within 8 weeks of 1st dose of study treatment. - Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. - Use of any prohibited medication within 14 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study treatment and during the study. - Prior use of any investigational or licensed anti-angiogenic agent, including topotecan, bevacizumab, thalidomide, and agents that target vascular endothelial growth factor (VEGF), VEGF receptors, or platelet-derived growth factor (PDGF). - Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia. - Known hypersensitivity to topoisomerase I inhibitors or pazopanib. - Administration of any non-oncologic investigational drug within 30 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment. |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | The West Clinic | Memphis | Tennessee |
| Lead Sponsor | Collaborator |
|---|---|
| Vector Oncology | GlaxoSmithKline |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Determine the maximum tolerated dose (MTD) of metronomic oral topotecan in combination with oral pazopanib for future phase II evaluation. | every 28 days | Yes | |
| Secondary | Identification and incidence of adverse events (AEs) and serious adverse events (SAEs). | every 28 days | Yes | |
| Secondary | Potential signals for response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 guidelines. | after every 2 cycles | No |