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

Alternate Title

UCN-01 and Irinotecan in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	JHOC-J0173 NCI-5528, NCT00047242, 5528

Objectives

1. Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and irinotecan in patients with advanced solid tumors, primarily lung, ovarian, and gastrointestinal tumors.
2. Determine the acute and chronic toxicity profile of this regimen in these patients.
3. Determine the pharmacokinetics of this regimen in these patients.
4. Determine, preliminarily, the anti-tumor effect of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative therapy does not exist or is no longer effective
  • Gastrointestinal, lung, and ovarian malignancies are given priority



• No brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior UCN-01 and irinotecan allowed

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No prior mediastinal radiation

Surgery

• Not specified

Other

• At least 14 days since prior warfarin
• No concurrent warfarin unless required for maintaining patency of existing, permanent IV catheters
• No concurrent commercial or other investigational anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 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 normal
• AST/ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic coronary artery disease
• No symptomatic cardiac dysfunction
• No symptoms suggestive of coronary artery disease
• LVEF at least 50%

Pulmonary

• No symptomatic pulmonary dysfunction
• FEV₁ greater than 75% of predicted
• DLCO greater than 75% of predicted

Other

• Amylase no greater than 2 times ULN
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No diabetes mellitus or random glucose more than 200 mg/dL
• No prior allergic reaction attributed to compounds of similar biological or chemical composition to UCN-01 or irinotecan (including rash and systemic allergic reaction causing hypotension and respiratory distress)
• No chronic diarrhea (more than 5 stools/day)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 14 days before, during, and for at least 30 days after study participation

Expected Enrollment

Approximately 20-30 patients will be accrued for this study within 7-15 months.

Outline

This is a dose-escalation study.

Patients receive UCN-01 IV over 3 hours on day 1 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 and irinotecan 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. At least 6 patients are treated at the recommended phase II dose.

Patients are followed at 1 month.

Jimeno A, Rudek MA, Purcell T, et al.: Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors. Cancer Chemother Pharmacol 61 (3): 423-33, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Ross Donehower, MD, Protocol chair		Ph: 410-955-8838 Email: donehro@jhmi.edu

Registry Information
Official Title		The Pharmacokinetic and Safety Profile of UCN-01 in Combination with Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)
Trial Start Date		2002-08-19
Trial Completion Date		2006-02-23
Registered in ClinicalTrials.gov		NCT00047242
Date Submitted to PDQ		2002-08-15
Information Last Verified		2006-04-08
NCI Grant/Contract Number		U01-CA70095, P30-CA06973

Back to Top