Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Topotecan in Treating Patients With Metastatic or Unresectable Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active 18 and over NCI NCI-05-C-0186 NCT00182676

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

1. Determine whether chronic administration of topotecan inhibits hypoxia inducible factor-1α (HIF-1α) in patients with metastatic or unresectable solid tumors expressing HIF-1α.

Secondary

1. Determine tumor angiogenesis using dynamic contrast-enhanced MRI in patients treated with this drug.
2. Determine the pharmacokinetics of this drug in these patients.
3. Determine tumor response in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior anticancer vaccines

Chemotherapy

• More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, mitomycin, or UCN-01)
• No concurrent chemotherapy

Endocrine therapy

• More than 4 weeks since prior anticancer hormonal therapy except gonadotropin-releasing hormone agonists
• Concurrent androgen suppression for the treatment of prostate cancer allowed

Radiotherapy

• More than 4 weeks since prior anticancer radiotherapy

Surgery

• Not specified

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• PT and PTT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 50 mL/min

Other

• 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

Expected Enrollment

A total of 13-20 patients will be accrued for this study within 2 years.

Outcomes

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

Outline

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 Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Giovanni Melillo, MD, Protocol chair		Ph: 301-846-5050
Shivaani Kummar, MD, Principal investigator		Ph: 301-435-5402 Email: kummars@exchange.nih.gov

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article
Web site for additional information

Registry Information
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		2008-11-30

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