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

Alternate Title

UCN-01 and Gemcitabine in Treating Patients With Unresectable or Metastatic Pancreatic Cancer

Basic Trial Information

Objectives

1. Determine the safety, toxicity profile, and maximum tolerated dose of UCN-01 and gemcitabine in patients with unresectable or metastatic adenocarcinoma of the pancreas.
2. Characterize the pharmacokinetic profile of this regimen in these patients.
3. Correlate various surrogate measurements of UCN-01 with intracellular concentrations in these patients.
4. Determine the recommended phase II dose of this regimen in these patients.
5. Determine the frequency, extent, and duration of any tumor responses in patients treated with this regimen.
6. Correlate serum alpha-1 acid glycoprotein levels in these patients with the pharmacokinetics and toxicity of UCN-01.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the pancreas

• Unidimensionally measurable disease
  • At least 20 mm by conventional techniques

    OR

  • At least 10 mm by spiral CT scan
  • Tumor lesions in a previously irradiated area are not considered measurable

• No known brain metastases
  • Patients with signs or symptoms of CNS metastasis at any time during screening must have a negative CT scan or MRI of the brain

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent over-the-counter biologics
• No concurrent growth factors during the first study course

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No more than 2 prior chemotherapy regimens (e.g., gemcitabine and/or experimental agents) alone or in combination with radiotherapy as neoadjuvant or adjuvant therapy for resectable, unresectable, or metastatic disease

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• See Chemotherapy
• At least 6 weeks since prior radiotherapy and recovered
• Prior radiotherapy directed only at the primary tumor bed allowed
• No prior radiotherapy to the mediastinum, pelvis, lower spine, or more than 20% of bone marrow

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery

Other:

• At least 4 weeks since prior investigational agents
• Concurrent enrollment in non-therapy trials (e.g., quality of life) allowed
• No concurrent herbal remedies
• No concurrent treatment for another active malignancy
• No concurrent warfarin for anticoagulation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial anticancer agents or therapies

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 greater than 100,000/mm³

Hepatic:

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

Renal:

• Creatinine normal

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No prior coronary artery disease
• No symptomatic cardiac dysfunction
• No prior myocardial infarction
• No active angina (even if controlled by medication)
• No positive stress test
• No uncontrolled arrhythmia
• Left ventricular ejection fraction at least 45%
• Patients with symptoms suggestive of coronary artery disease or arrhythmia must have no evidence of cardiac pathology

Pulmonary:

• No symptomatic pulmonary dysfunction

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to UCN-01 or other study agents
• No insulin-dependent diabetes mellitus
• No other concurrent uncontrolled illness
• No ongoing or active infections
• No concurrent psychiatric illness
• No other active malignancy
• No other solid tumor within the past 5 years except neoplasia in situ or nonmelanomatous skin cancer
• No social situations that would preclude study compliance

Expected Enrollment

Approximately 6-30 patients will be accrued for this study within 2-15 months.

Outline

This is a dose-escalation study.

Patients receive gemcitabine IV over 1-2 hours on days 1 and 8 followed by UCN-01 IV over 3 hours on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of UCN-01 is followed by sequential dose escalation of gemcitabine. Cohorts of 3-6 patients receive escalating doses of UCN-01 and then gemcitabine until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 patients are treated at the recommended phase II dose.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Linus Ho, MD, Protocol chair		Ph: 713-792-2828; 800-392-1611 Email: linusho@mdanderson.org

Registry Information
Official Title		A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma
Trial Start Date		2002-05-31
Registered in ClinicalTrials.gov		NCT00039403
Date Submitted to PDQ		2002-04-22
Information Last Verified		2006-01-17
NCI Grant/Contract Number		CA16672, CA62461

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