Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial
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)
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.
Status | Completed |
Enrollment | 41 |
Est. completion date | |
Est. primary completion date | January 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - 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 |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of Virginia | Charlottesville | Virginia |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) | Washington University Siteman Cancer Center |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Yes |
Primary | DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I) | Part I | Yes | |
Primary | 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 | Yes |
Primary | 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 | No |
Primary | 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 | No |
Secondary | 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 | No |
Secondary | 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 | No |
Secondary | Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations | Weekly during the first 4 weeks of course 1 | No | |
Secondary | 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 | No |
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