Topotecan in Treating Patients With Gynecologic Cancer That Cannot Be Removed by Surgery

Ovarian Cancer Clinical Trial

Official title:

A Phase I Study of Weekly Oral Topotecan in Gynecologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00842452
• Other study ID #: CASE2Y08
• Secondary ID: P30CA043703CASE2
• Status: Completed
• Phase: Phase 1
• First received: February 11, 2009
• Last updated: April 3, 2013
• Start date: February 2009
• Est. completion date: April 2011

Study information

• Verified date: April 2013
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cervical Cancer
• Endometrial Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Sarcoma
• Uterine Cervical Neoplasms
• Vaginal Cancer
• Vaginal Neoplasms
• Vulvar Cancer
• Vulvar Neoplasms

Intervention

Drug:
• topotecan hydrochloride
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.

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

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Steven Waggoner, MD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)		Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.	Yes
Primary	Safety and tolerability		Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.	Yes
Primary	Plasma concentration of topotecan hydrochloride when administered at the MTD		blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies	No
Secondary	Response		Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.	No