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

Alternate Title

KRN5500 in Treating Patients With Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	DFCI-00102 NCI-1653, NCT00017238, 1653

Objectives

Primary

1. Determine the maximum tolerated dose and dose-limiting toxic effects of KRN5500 in patients with solid tumors.
2. Assess the safety of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.
4. Determine the response, by 3'deoxy- 3'fluorothymidine positron emission tomography scan, of a subset of patients treated with this drug.

Secondary

1. Determine, preliminarily, the antitumor activity of this drug in these patients.
2. Determine pharmacodynamic relationships for the pharmacological effect of this drug upon surrogate markers of activity and toxicity in these patients.
3. Compare the toxicity profiles for the 1-hour and 72-hour infusion administration schedules of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Metastatic or inoperable malignancy for which there is no known curative or survival-prolonging palliative therapy or that has failed all such therapies
  • No leukemia or primary CNS tumors



• No active brain metastases, including:
  • No evidence of cerebral edema by CT scan or MRI
  • No progression from prior imaging study
  • No requirement for steroids
  • No related clinical symptoms

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since prior major surgery

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No uncontrolled or significant cardiac disease
• No myocardial infarction within the past 6 months
• No significant congestive heart failure
• No prior clinically significant atrial or ventricular arrhythmia
• No prior second- or third-degree heart block
• No evidence of acute ischemia or prolonged QTc interval (greater than 450 ms) on electrocardiogram

Pulmonary:

• No uncontrolled or significant pulmonary disease

Other:

• No serious uncontrolled medical disorder that would preclude study participation
• No active infection
• No psychiatric illness that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 20-40 patients will be accrued for this study within 9-12 months.

Outline

This is a dose-escalation, multicenter study.

Patients receive KRN5500 IV over 24-72 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-3 patients receive KRN5500 at the starting dose over escalating infusion durations. After the longest duration of infusion time is safely reached, cohorts of 3-6 patients receive escalating doses of KRN5500 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with KRN5500 at the recommended phase II dose.

Patients are followed every 4 weeks until resolution of all toxicity.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Joseph Paul Eder, MD, Protocol chair		Ph: 617-632-5588; 866-790-4500 Email: joseph_eder@dfci.harvard.edu

Registry Information
Official Title		A Phase I Trial Of KRN5500 (NSC 650426) Given As 72 Hour Continuous IV Infusion Every 21 Days In Patients With Solid Tumors
Trial Start Date		2001-06-12
Registered in ClinicalTrials.gov		NCT00017238
Date Submitted to PDQ		2001-04-12
Information Last Verified		2004-11-22
NCI Grant/Contract Number		P30-CA06516, U01-CA62490

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