UCN-01 And Gemcitabine In Treating Patients With Unresectable Or Metastatic Pancreatic Cancer

Study Overview

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

Phase I trial to study the effectiveness of combining UCN-01 with gemcitabine in treating patients who have unresectable or metastatic pancreatic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may help gemcitabine kill more cancer cells by making tumor cells more sensitive to the drug

PRIMARY OBJECTIVES: I. To determine the safety and toxicity profile of UCN-01 when given in combination with gemcitabine to patients with unresectable or metastatic adenocarcinoma of the pancreas. II. To characterize the pharmacokinetic profiles of gemcitabine and UCN-01 when given in combination and to correlate various measurements of UCN-01 with intracellular concentrations. III. To determine recommended doses of UCN-01 and gemcitabine in combination to be used in a planned subsequent phase II trial. SECONDARY OBJECTIVES: I. To record the frequency, extent, and duration of any tumor responses. II. To correlate serum alpha-1 acid glycoprotein (AGP) levels with UCN-01 pharmacokinetics and toxicity. 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.

Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer

DRUG: 7-hydroxystaurosporine
DRUG: gemcitabine hydrochloride
OTHER: pharmacological study
OTHER: laboratory biomarker analysis

NCI-2012-02468
DM01-553
U01CA062461 (U.S. NIH Grant/Contract)
CDR0000069380 (REGISTRY Identifier) (REGISTRY: PDQ (Physician Data Query))

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2002-06-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-01-22
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-01-23
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2013-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (UCN-01, gemcitabine hydrochloride) 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 s	DRUG: 7-hydroxystaurosporine Given IV DRUG: gemcitabine hydrochloride Given IV OTHER: pharmacological study Correlative studies OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (UCN-01, gemcitabine hydrochloride)

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 s

DRUG: 7-hydroxystaurosporine

Given IV

DRUG: gemcitabine hydrochloride

Given IV

OTHER: pharmacological study

Correlative studies

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Incidence of toxicity		Up to 4 years
Pharmacokinetic profiles		Weeks 1-6 for UCN-01 and weeks 1 and 4 for intracellular gemcitabine
Recommended phase II doses		3 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Frequency, extent, and duration of any tumor responses		Up to 4 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the pancreas
Unidimensionally measurable disease

At least 20 mm by conventional techniques
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
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 3 months
WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count greater than 100,000/mm^3
Bilirubin no greater than 1.5 mg/dL
ALT and AST no greater than 2.5 times upper limit of normal
Creatinine normal
Creatinine clearance at least 60 mL/min
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
No symptomatic pulmonary dysfunction
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
No concurrent over-the-counter biologics
No concurrent growth factors during the first study course
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
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
At least 4 weeks since prior major surgery
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Linus Ho, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record