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

NCT00842452 | Completed Phase 1 DMC

• 4 other identifiers: CASE2Y08P30CA043703CASE 2Y08-CC630NCI-2009-01290
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.

• Safety and tolerability

  Treatment repeats every 28 days for up to 6 courses in the absence of unacceptable toxicity.

• Plasma concentration of topotecan hydrochloride when administered at the MTD

  blood sample collection periodically on day 1 of course 1 for pharmacokinetic studies

Secondary Outcomes (1)

• Response

  Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.

Study Arms (1)

Oral Topotecan

EXPERIMENTAL

Drug: topotecan hydrochloride; Other: pharmacological study

Interventions

topotecan hydrochloride DRUG

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.

Oral Topotecan

pharmacological study OTHER

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

Oral Topotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Steven Waggoner, MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Endometrial Neoplasms; Fallopian Tube Neoplasms; Ovarian Neoplasms; Sarcoma; Vaginal Neoplasms; Vulvar Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Fallopian Tube Diseases; Adnexal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Vaginal Diseases; Vulvar Diseases; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Stephen Waggoner, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2009
• First Posted: February 12, 2009
• Study Start: February 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 5, 2013

Record last verified: 2013-04

Locations

US (1)