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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

Phase 1
18 Years
Open (Enrolling)
Gynecologic Tumors

Thank you

Trial Information

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. 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 Accelerated Community Oncology Research
Network, Inc.(ACORN) site and will include approximately 9-20 evaluable patients. Treatment
cycle length is 28 days. During cycle 1, patients will have assessments done on days 1, 8,
and 15. During cycle 2 and in subsequent cycles, patients will have assessments done on days
1 and 15. The patient may be evaluated more frequently as needed to manage toxicities or
per investigator discretion. Radiologic imaging will be repeated after every 2 cycles.

Inclusion Criteria:

- Subjects must provide written informed consent prior to the performance of study
specific procedures or assessments, and must be willing to comply with treatment and

- Female patients, greater than 18 years of age with recurrent or persistent
gynecologic tumor including ovarian, primary peritoneal, fallopian tube, cervical
cancer, and any other appropriate gynecologic tumor

- 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

- GOG performance status of 0,1,or 2

- Must have a life expectancy of at least six months

- Adequate bone marrow, liver and renal function at study entry as assessed by the

- 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. If dipstick > 2+ or UPC > 1, then
a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine
protein value < 1 g to be eligible.

- A female is eligible to enter and participate in this study if she is of:
Non-childbearing potential OR is post-menopausal.

Exclusion Criteria:

- 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.

- Whole pelvic or extended field radiation therapy within 45 days of first dose of
study treatment and/or concurrent radiotherapy treatment during study participation.

- 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

- 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 suspected 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

- 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. Blood pressure must be re-assessed on two occasions that are separated
by a minimum of 24 hours. The mean SBP/DBP values from each blood pressure assessment
must be <140/90 mmHg in order for a subject to be eligible for the study.

- History of cerebrovascular accident, 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; however, the
use of therapeutic levels of warfarin must have ended more than 14 days prior to
first dose of study treatment.

- Evidence of active bleeding or bleeding diathesis.

- 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 prior to the first dose of study
treatment(see Section 4.8.2).

- Prior use of any investigational or licensed anti-angiogenic agent, including
topotecan,bevacizumab, thalidomide, and agents that target VEGF, VEGF receptors, or

- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is
progressing in severity.

- Known hypersensitivity to topoisomerase I inhibitors or pazopanib.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the MTD of metronomic oral topotecan in combination with oral pazopanib for future phase II evaluation.

Outcome Time Frame:

every 28 days

Safety Issue:


Principal Investigator

Todd D Tillmanns, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The West Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

December 2013

Related Keywords:

  • Gynecologic Tumors
  • Gynecologic tumors
  • Genital Neoplasms, Female



The West Clinic Memphis, Tennessee  38120