Topotecan in Treating Patients With Metastatic or Unresectable Solid Tumors
|Phase I||Treatment||Closed||18 and over||NCI||NCI-05-C-0186|
Special Category: NCI Web site featured trial
- Determine whether chronic administration of topotecan inhibits hypoxia inducible factor-1α (HIF-1α) in patients with metastatic or unresectable solid tumors expressing HIF-1α.
- Determine tumor angiogenesis using dynamic contrast-enhanced MRI in patients treated with this drug.
- Determine the pharmacokinetics of this drug in these patients.
- Determine tumor response in patients treated with this drug.
- Histologically confirmed solid tumor
- Metastatic or unresectable disease
- Progressive disease after prior standard therapy OR no standard therapy exists
- Hypoxia inducible factor-1α (HIF-1α)-expressing tumor by immunohistochemistry, defined as > 10% of cells staining positive for HIF-1α
- Tumor accessible by biopsy with minimal or small amount of risk to the patient
- No known brain metastases
- Previously treated brain metastases that have remained stable for ≥ 4 months without steroids or antiseizure medication allowed at the discretion of the investigator
- More than 4 weeks since prior anticancer vaccines
- More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, mitomycin, or UCN-01)
- No concurrent chemotherapy
- More than 4 weeks since prior anticancer hormonal therapy except gonadotropin-releasing hormone agonists
- Concurrent androgen suppression for the treatment of prostate cancer allowed
- More than 4 weeks since prior anticancer radiotherapy
- Not specified
- Recovered from prior therapy
- No prior topotecan
- At least 2 weeks since prior and no other concurrent investigational agents administered as part of a phase 0 study
- No concurrent herbal or alternative medications except a single daily multivitamin
- 18 and over
- More than 3 months
- WBC ≥ 3,000/mm3
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- PT and PTT ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No known HIV positivity
- No known immune deficiency syndrome
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to topotecan or to any component of the topotecan formulation
- No active peptic ulcer or gastrointestinal condition that could alter absorption or motility
- No other unstable medical illness
A total of 13-20 patients will be accrued for this study within 2 years.
Modulation of hypoxia inducible factor-1α expression at baseline, week 2, and week 6
Tumor response by CT scan at baseline and week 8
Tumor metabolism and angiogenesis by DCE-MRI at baseline, week 2, and week 6
This is a pilot study.
Patients receive oral topotecan once daily on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients who are in remission are followed every 3 months until the start of salvage therapy.
Trial Lead Organizations
NCI - Center for Cancer Research
|Giovanni Melillo, MD, Protocol chair|
|Shivaani Kummar, MD, Principal investigator|
|Official Title||A Pilot Trial of Oral Topotecan for the Treatment of Refractory Advanced Solid Neoplasms Expressing HIF-1α|
|Trial Start Date||2005-07-05|
|Trial Completion Date||2008-12-02 (estimated)|
|Registered in ClinicalTrials.gov||NCT00182676|
|Date Submitted to PDQ||2005-07-05|
|Information Last Verified||2009-06-14|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.