7-Hydroxystaurosporine And Irinotecan Hydrochloride In Treating Patients With Metastatic Or Unresectable Solid Tumors Or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

Study Overview

7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

This phase I trial is studying the side effects and best dose of giving 7-hydroxystaurosporine together with irinotecan hydrochloride in treating patients with metastatic or unresectable solid tumors, including triple-negative breast cancer (currently enrolling only patients with triple-negative breast cancer since 6/8/2007). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving 7-hydroxystaurosporine together with irinotecan hydrochloride may help kill more cancer cells by making tumor cells more sensitive to the drug.

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of UCN-01 (7-hydroxystaurosporine) and irinotecan (irinotecan hydrochloride) in patients with resistant solid tumors. (Part I [closed to accrual as of 6/8/2007]) II. Determine the dose-limiting toxicity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. Determine the types of toxic effects of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) IV. 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) V. Determine the side effect profile of this regimen in patients with triple negative recurrent breast cancer. (Part II) SECONDARY OBJECTIVES: I. Determine any anti-tumor activity of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) II. Determine the pharmacokinetics of this regimen in these patients. (Part I [closed to accrual as of 6/8/2007]) III. 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]) IV. Determine the in vivo mechanisms of UCN-01 activity in these patients. OUTLINE: This is a dose-escalation study. PART I: Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine 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 hydrochloride and 7-hydroxystaurosporine 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 hydrochloride IV and 7-hydroxystaurosporine IV as in part I at the MTD and undergo blood sample collection.

Advanced Adult Primary Liver Cancer
Carcinoma of the Appendix
Estrogen Receptor-negative Breast Cancer
Extensive Stage Small Cell Lung Cancer
Gastrointestinal Stromal Tumor
HER2-negative Breast Cancer
Metastatic Gastrointestinal Carcinoid Tumor
Ovarian Sarcoma
Ovarian Stromal Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Adult Primary Liver Cancer
Recurrent Anal Cancer
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
Recurrent Breast Cancer
Recurrent Cervical Cancer
Recurrent Colon Cancer
Recurrent Endometrial Carcinoma
Recurrent Esophageal Cancer
Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Recurrent Extrahepatic Bile Duct Cancer
Recurrent Gallbladder Cancer
Recurrent Gastric Cancer
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Non-small Cell Lung Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Ovarian Germ Cell Tumor
Recurrent Pancreatic Cancer
Recurrent Prostate Cancer
Recurrent Rectal Cancer
Recurrent Salivary Gland Cancer
Recurrent Small Cell Lung Cancer
Recurrent Small Intestine Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Small Intestine Adenocarcinoma
Small Intestine Leiomyosarcoma
Small Intestine Lymphoma
Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
Stage IV Anal Cancer
Stage IV Basal Cell Carcinoma of the Lip
Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor
Stage IV Breast Cancer
Stage IV Colon Cancer
Stage IV Endometrial Carcinoma
Stage IV Esophageal Cancer
Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IV Gastric Cancer
Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Lymphoepithelioma of the Oropharynx
Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
Stage IV Non-small Cell Lung Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Ovarian Germ Cell Tumor
Stage IV Pancreatic Cancer
Stage IV Prostate Cancer
Stage IV Rectal Cancer
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Stage IVA Cervical Cancer
Stage IVB Cervical Cancer
Triple-negative Breast Cancer
Unresectable Extrahepatic Bile Duct Cancer
Unresectable Gallbladder Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Untreated Metastatic Squamous Neck Cancer With Occult Primary

DRUG: 7-hydroxystaurosporine
DRUG: irinotecan hydrochloride
OTHER: diagnostic laboratory biomarker analysis

NCI-2009-00019
NCI-2009-00019 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
NCI-5582
WUSM-SCC-0102
CDR0000069215
UVACC-SCC-0102
SCC 01-02 (OTHER Identifier) (OTHER: University of Virginia)
5582 (OTHER Identifier) (OTHER: CTEP)
P30CA044579 (U.S. NIH Grant/Contract)

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 2002-03-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-09-27
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-09-30
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2013-09

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 (combination chemotherapy) PART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts	DRUG: 7-hydroxystaurosporine Given IV DRUG: irinotecan hydrochloride Given IV OTHER: diagnostic laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (combination chemotherapy)

PART I: Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, and 22 and 7-hydroxystaurosporine IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts

DRUG: 7-hydroxystaurosporine

Given IV

DRUG: irinotecan hydrochloride

Given IV

OTHER: diagnostic laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)	Defined as the highest dose given to at least 6 patients in which =< 1 out of 6 experience dose limiting toxicity (DLT).	Part I
DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)		Part I
Toxicities associated with irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)	Graded using the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).	Continuously over study treatment
Anti-tumor activity of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in ER-negative, PgR-negative, HER-2 not-amplified (triple negative) recurrent breast cancer (Part II)	Including overall response rate (partial response [PR] +complete response [CR]), clinical benefit rate (PR+CR+stable disease [SD]), and time to disease progression. 95% confidence interval will be calculated. Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.	Every 6 weeks
Side effect profile of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in triple negative recurrent breast cancer (Part II)	95 % confidence interval will be calculated.	Continuously over study treatment

Secondary Outcome Measures	Measure Description	Time Frame
Anti-tumor activity of the combination of irinotecan hydrochloride and 7-hydroxystaurosporine in treatment of patients with resistant solid tumor malignancies	Evaluated by the RECIST criteria.	Every 6 weeks
Pharmacokinetics of irinotecan hydrochloride and 7-hydroxystaurosporine when administered in combination	Using the high-performance liquid chromatography (HPLC) assays.	Weekly during the first 4 weeks of course 1
Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations		Weekly during the first 4 weeks of course 1
In vivo mechanistic basis for 7-hydroxystaurosporine activity	Explored by subgroup analysis (responders versus non-responders) on pharmacodynamic measures.	Weekly during the first 4 weeks of course 1

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:

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
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 12 weeks
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
Bilirubin normal
AST/ALT no greater than 3 times upper limit of normal (ULN)
No Gilbert's disease
No chronic unconjugated hyperbilirubinemia
Creatinine no greater than 1.5 times ULN
Creatinine clearance at least 60 mL/min
No symptomatic cardiac dysfunction
No symptomatic pulmonary dysfunction
Oxygen saturation at least 90% by pulse oximetry on room air at rest and after walking 6 minutes
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
No concurrent granulocyte colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study
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)
More than 4 weeks since prior radiotherapy and recovered
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

Collaborators and Investigators

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

Washington University Siteman Cancer Center

Investigators

PRINCIPAL_INVESTIGATOR: Paula Fracasso, University of Virginia

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

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