Phase I Trial of Oral Metronomic Topotecan and Oral Pazopanib to Treat Recurrent/Persistent Gynecologic Tumors
This study is currently recruiting participants.
Verified January 2014 by Accelerated Community Oncology Research Network
Information provided by (Responsible Party):
Accelerated Community Oncology Research Network
First received: December 1, 2008
Last updated: January 6, 2014
Last verified: January 2014
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors.
Drug: Oral Topotecan
||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Determine the MTD of metronomic oral topotecan in combination with oral pazopanib for future phase II evaluation. [ Time Frame: every 28 days ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Identification and incidence of AEs and SAEs. [ Time Frame: every 28 days ] [ Designated as safety issue: Yes ]
- Potential signals for response per RECIST criteria. [ Time Frame: after every 2 cycles ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2014 (Final data collection date for primary outcome measure)
Metronomic oral topotecan and oral pazopanib will be administered by mouth beginning on Cycle 1 Day 1. Patients will be enrolled and observed for DLT(s) for 1 cycle of treatment. Dose modification of the combination will depend on the number of patients experiencing DLT(s) at each dose level.
Drug: Oral Topotecan
Starting on Cycle 1 Day 1, each subject will receive the assigned dose of topotecan administered by mouth.
Other Name: Hycamtin capsules
Starting on Cycle 1 Day 1, each subject will receive the assigned dose of pazopanib administered by mouth.
This is a Phase 1, dose-escalation study in female patients with recurrent or persistent gynecologic tumors. The study will include a Screening Phase, a Treatment Phase and a Followup Phase. In the Screening Phase the subject's eligibility for study participation will be determined; this phase can last up to 28 days. The Treatment Phase will begin when the subject starts study treatment and will continue until the subject is removed from study treatment. The Follow-up Phase will last for 30 days after the subject ends study treatment. The study will be conducted at approximately 1 site and will include approximately 41 evaluable patients. Treatment cycle length is 28 days. Radiologic imaging will be repeated after every 2 cycles of treatment.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- 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.
- ANC ≥ 1.5 x 10^9/L.
- Platelet count ≥ 100 x 10^9/L.
- PT or INR < 1.2 x ULN.
- PTT < 1.2 x ULN.
- Total bilirubin ≤ 1.5 x ULN.
- ALT and 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 UPC < 1.0.
- LVEF ≥ 50% or the institutional LLN
- Patients must be physiologically incapable of becoming pregnant, be postmenopausal, or have a negative pregnancy test and agree to use adequate contraception.
- 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 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 QTc > 480 msecs.
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 NYHA
- Poorly controlled hypertension (defined as SBP of > 140 mmHg or DBP 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 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.
- 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 VEGF, VEGF receptors, or 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00800345
|The West Clinic
|Memphis, Tennessee, United States, 38120 |
|Principal Investigator: Todd D Tillmanns, MD |
Accelerated Community Oncology Research Network
||Todd D Tillmanns, MD
||The West Clinic
No publications provided
||Accelerated Community Oncology Research Network
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 1, 2008
||January 6, 2014
||United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Accelerated Community Oncology Research Network:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 06, 2014
Genital Neoplasms, Female
Neoplasms by Site
Topoisomerase I Inhibitors
Molecular Mechanisms of Pharmacological Action