Patient case: 26-year-old female with Cervical cancer. Genetic variant: STK11. Other conditions: None.

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

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: 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

Relevance to patient case: not relevant