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UCN-01 and Irinotecan in Treating Patients With Metastatic or Unresectable Solid Tumors

This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), March 2008

Sponsors and Collaborators: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00031681
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving UCN-01 together with irinotecan may help kill more cancer cells by making tumor cells more sensitive to the drug.

PURPOSE: This phase I trial is studying the side effects and best dose of giving UCN-01 together with irinotecan in treating patients with metastatic or unresectable solid tumors.


Condition Intervention Phase
Cancer
Drug: 7-hydroxystaurosporine
Drug: irinotecan hydrochloride
Procedure: laboratory biomarker analysis
Phase I

Genetics Home Reference related topics:   breast cancer   

MedlinePlus related topics:   Breast Cancer    Cancer    Lung Cancer   

ChemIDplus related topics:   Irinotecan    Irinotecan hydrochloride    UCN 01    Salicylsalicylic acid    Sodium salicylate   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
Official Title:   A Phase I Study Of UCN-01 In Combination With Irinotecan In Resistant Solid Tumor Malignancies (Part I) and in Triple Negative (ER-Negative, PgR-Negative, HER-2 Not Amplified) Recurrent Breast Cancers (Part II)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Anti-tumor activity (overall response rate [partial response and complete response], clinical benefit rate [partial response, complete response, and stable disease], and time to disease progression) [ Designated as safety issue: No ]
  • Side effect profile [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • In vivo mechanisms [ Designated as safety issue: No ]

Estimated Enrollment:   41
Study Start Date:   December 2001
Estimated Primary Completion Date:   July 2002 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of UCN-01 and irinotecan in patients with resistant solid tumors. (Part I [closed to accrual as of 6/8/2007])
  • Determine the dose-limiting toxicity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007])
  • Determine the types of toxic effects of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007])
  • Determine the anti-tumor activity in terms of overall response rate (partial response [PR] and complete response [CR]), clinical benefit rate (PR, CR, and stable disease), and time to disease progression in patients with estrogen receptor-negative, progesterone receptor-negative, and HER-2 not amplified (triple negative) locally recurrent or metastatic breast cancer treated with this regimen. (Part II)
  • Determine the side effect profile of this regimen in patients with triple negative recurrent breast cancer. (Part II)

Secondary

  • Determine any anti-tumor activity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007])
  • Determine the pharmacokinetics of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007])
  • Determine the activity of the serum α-acid glycoprotein and correlate this level with free UCN-01 concentrations. (Part I [closed to accrual as of 6/8/2007])
  • Determine the in vivo mechanisms of UCN-01 activity in these patients.

OUTLINE:

  • Part I (treatment of resistant solid tumors [closed to accrual as of 6/8/2007]):

This is a dose-escalation study.

Patients receive irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and UCN-01 IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan and UCN-01 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.

Blood samples are collected periodically during study treatment.

  • Part II (treatment of triple negative recurrent breast cancer):

Patients receive irinotecan IV and UCN-01 IV as in part I at the MTD and undergo blood sample collection.

PROJECTED ACCRUAL: A total of 41 patients (21 part I [closed to accrual as of 6/8/2007] and 20 part II) will be accrued for this study.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • Part I (closed to accrual as of 6/8/2007)

    • Histologically confirmed solid tumor that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective, including the following:

      • Gastrointestinal tract cancer
      • Lung cancer
      • Breast cancer
      • Ovarian cancer
      • Endometrial cancer
      • Cervical cancer
      • Prostate cancer
      • Head and neck cancer
    • Patients with or without measurable or evaluable disease allowed

      • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by conventional techniques or ≥ 10 mm with spiral CT scan

        • Tumor markers allowed for evaluable disease
        • Positive bone scan, osteoblastic metastases, and pleural or peritoneal effusions are not considered measurable or evaluable disease
    • No known brain metastases
  • Part II

    • Histologically confirmed (either primary or the recurrent site) locally recurrent or metastatic breast cancer not amendable to surgery

      • Measurable disease

        • For skin lesions, documentation by color photography and estimation of lesion size with a ruler are required
    • Must have undergone prior therapy with an anthracycline and a taxane either in the adjuvant or metastatic setting
    • CNS metastasis allowed provided stable disease (i.e., no evidence of local progression) ≥ 3 months after local therapy
    • Hormone receptor status:

      • Estrogen receptor negative
      • Progesterone receptor negative
      • HER-2 not amplified by fluorescence in situ hybridization

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Not specified

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • More than 12 weeks

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL

Hepatic:

  • Bilirubin normal
  • AST/ALT no greater than 3 times upper limit of normal (ULN)
  • No Gilbert's disease
  • No chronic unconjugated hyperbilirubinemia

Renal:

  • Creatinine no greater than 1.5 times ULN OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No symptomatic cardiac dysfunction

Pulmonary:

  • No symptomatic pulmonary dysfunction
  • Oxygen saturation at least 90% by pulse oximetry on room air at rest and after walking 6 minutes

Other:

  • No insulin-dependent diabetes mellitus
  • No other uncontrolled concurrent illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study entry
  • No prior allergic reactions attributed to compounds of similar chemical or biological composition to UCN-01 or irinotecan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent granulocyte colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study

Chemotherapy:

  • See Disease Characteristics (Part II)
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior irinotecan allowed
  • Less than 4 prior chemotherapy regimens in the adjuvant and/or metastatic setting (Part II)

Endocrine therapy:

  • Not specified

Radiotherapy:

  • More than 4 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified

Other:

  • Concurrent warfarin allowed
  • Concurrent subcutaneous heparin allowed
  • No other concurrent investigational agents
  • No concurrent anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00031681

Locations
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis     Recruiting
      Saint Louis, Missouri, United States, 63110
      Contact: Cynthia X. Ma, MD, PhD     314-362-8903        
United States, Virginia
University of Virginia Cancer Center     Recruiting
      Charlottesville, Virginia, United States, 22908-0466
      Contact: Paula M. Fracasso, MD, PhD     434-243-6143        

Sponsors and Collaborators
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
National Cancer Institute (NCI)

Investigators
Study Chair:     Paula M. Fracasso, MD, PhD     University of Virginia    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000069215, WUSM-SCC-0102, NCI-5582
First Received:   March 8, 2002
Last Updated:   August 2, 2008
ClinicalTrials.gov Identifier:   NCT00031681
Health Authority:   Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer  
stage IV breast cancer  
recurrent breast cancer  
stage IV gastric cancer  
recurrent gastric cancer  
recurrent non-small cell lung cancer  
recurrent pancreatic cancer  
stage IV rectal cancer  
recurrent colon cancer  
recurrent rectal cancer  
stage IV anal cancer  
recurrent anal cancer  
stage IV esophageal cancer  
recurrent esophageal cancer  
recurrent cervical cancer  
stage IVB cervical cancer
stage IVA cervical cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
advanced adult primary liver cancer
recurrent adult primary liver cancer
stage IV endometrial carcinoma
recurrent endometrial carcinoma
small intestine adenocarcinoma
small intestine lymphoma
small intestine leiomyosarcoma

Study placed in the following topic categories:
Pancreatic Neoplasms
Malignant mesenchymal tumor
Ovarian epithelial cancer
Carcinoma, Adenoid Cystic
Lung Neoplasms
Metastatic squamous neck cancer with occult primary
Staurosporine
Laryngeal carcinoma
Salivary Gland Diseases
Rectal cancer
Non-small cell lung cancer
Breast Neoplasms
Carcinoma, Basal Cell
Stomach cancer
7-hydroxystaurosporine
Camptothecin
Carcinoma
Gall bladder cancer
Carcinoma, Small Cell
Sarcoma
Carcinoid Tumor
Esophageal Diseases
Carcinoma, Squamous Cell
Anus Neoplasms
Prostatic Neoplasms
Carcinoma, Non-Small-Cell Lung
Leiomyosarcoma
Esophageal Neoplasms
Squamous cell carcinoma
Irinotecan

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 10, 2008




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