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A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma

Phase 1
18 Years
Not Enrolling
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

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Trial Information

A Phase I Study Of UCN-01 In Combination With Gemcitabine In Unresectable Or Metastatic Pancreatic Carcinoma


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

III. To determine recommended doses of UCN-01 and gemcitabine in combination to be used in a
planned subsequent phase II trial.


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

- 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

- 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:


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:


Principal Investigator

Linus Ho

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




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



M D Anderson Cancer Center Houston, Texas  77030