Clinical trial NCT00842452: Topotecan in Treating Patients With Gynecologic Cancer That Cannot Be Removed by Surgery
Official title: A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Endometrial Cancer
Fallopian Tube Cancer
Ovarian Cancer
Sarcoma
Vaginal Cancer
Vulvar Cancer
Keywords: recurrent ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent uterine sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
recurrent vaginal cancer
stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
recurrent vulvar cancer
stage III vulvar cancer
stage IV vulvar cancer
recurrent cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
fallopian tube cancer
ovarian sarcoma
ovarian stromal cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-02-12
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of topotecan in treating patients with gynecologic cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To establish the maximum tolerated dose (MTD) of oral topotecan hydrochloride in patients with unresectable gynecologic malignancies.
* To determine the safety and tolerability of this drug in these patients.
* To obtain pharmacokinetic data to assess plasma concentrations of this drug when administered at the MTD.

Secondary

* To explore the response in patients treated with this drug.

OUTLINE: Patients receive oral topotecan hydrochloride on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients treated at the maximum tolerated dose undergo blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically\* or cytologically confirmed unresectable gynecologic malignancy for which standard curative or palliative care is not available

  * All tumor types allowed NOTE: \*Histologic confirmation of recurrence is not required
* Measurable or nonmeasurable disease

  * If CT scan was used to evaluate measurable disease, lesions must be clearly defined and be ≥ 10 mm on spiral CT scan
* No "borderline tumors" or tumors with low malignant potential

PATIENT CHARACTERISTICS:

* Karnofsky performance status 60-100%
* Life expectancy ≥ 12 weeks
* ANC ≥ 1,500/μL
* Platelet count ≥ 100,000/μL
* Hemoglobin ≥ 9 g/dL
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Creatinine clearance ≥ 60 mL/min
* AST/ALT ≤ 2.5 times ULN (\< 5 times ULN if liver metastases are present)
* Alkaline phosphatase ≤ 2.5 times ULN (\< 5 times ULN if liver metastases are present)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Adequate intestinal function (i.e., no gastrostomy tube or requirement for IV hydration or nutritional support)
* No severe gastrointestinal bleeding or intestinal obstruction
* No other condition that would affect gastrointestinal absorption and motility
* No septicemia, severe infection, or acute hepatitis
* No other malignancies requiring chemotherapy or radiotherapy within the past 5 years, except skin cancer
* No concurrent severe medical problem unrelated to the malignancy that would significantly limit full compliance with the study, expose the patient to extreme risk, or decrease life expectancy

PRIOR CONCURRENT THERAPY:

* At least 28 days since prior investigational drugs (including cytotoxic drugs)
* At least 4 weeks since prior chemotherapy, radiotherapy, biologic therapy, or surgery and recovered
* No more than 3 prior chemotherapy regimens
* No prior topotecan hydrochloride or other camptothecin analogs
* No prior radiotherapy to \> 25% of the bone marrow
* No other concurrent chemotherapy, radiotherapy, biologic therapy, immunotherapy, or hormonal therapy for cancer
* No concurrent administration of any of the following:

  * P-glycoprotein (ABCB1, Pgp, MDR1) inhibitors or inducers
  * Breast cancer-resistant protein (ABCG2, BCRP, MXR) inhibitors or inducers
* No concurrent chronic H2 antagonists, proton pump inhibitors, or antacids for gastritis, gastroesophageal reflux disease, or gastric or duodenal ulcers

  * Intermittent antacid therapy is allowed provided it is given ≥ 6 hours prior to and ≥ 90 minutes after study drug administration

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.
measure: Safety and tolerability
timeFrame: Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.
measure: Plasma concentration of topotecan hydrochloride when administered at the MTD
timeFrame: blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies
Secondary outcomes:
measure: Response
timeFrame: Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Stephen Waggoner, MD
role: PRINCIPAL_INVESTIGATOR
References: