A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma
18 Years
N/A
Both
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer
Trial Information
A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma
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.
Inclusion Criteria:
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of toxicity
Outcome Time Frame:
Up to 4 years
Safety Issue:
Yes
Principal Investigator
Linus Ho
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02468
NCT ID:
NCT00039403
Start Date:
April 2002
Completion Date:
Related Keywords:
- Adenocarcinoma of the Pancreas
- Recurrent Pancreatic Cancer
- Stage II Pancreatic Cancer
- Stage III Pancreatic Cancer
- Stage IV Pancreatic Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Pancreatic Neoplasms
Name | Location |
|---|---|
| M D Anderson Cancer Center | Houston, Texas 77030 |
