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)

Condition(s): Cancer Unspecified Adult Solid Tumor, Protocol Specific Estrogen Receptor-negative Breast Cancer Progesterone Receptor-negative Breast Cancer Stage IV Breast Cancer Recurrent Breast Cancer Stage IV Colon Cancer Recurrent Colon Cancer Stage IV Prostate Cancer Recurrent Prostate Cancer Gastrointestinal Stromal Tumor Carcinoma of the Appendix Extensive Stage Small Cell Lung Cancer Recurrent Pancreatic Cancer Recurrent Rectal Cancer Stage IV Rectal Cancer Stage IV Non-Small Cell Lung Cancer Recurrent Small Cell Lung Cancer Recurrent Non-Small Cell Lung Cancer Ovarian Sarcoma Recurrent Ovarian Epithelial Cancer Recurrent Ovarian Germ Cell Tumor Stage IV Ovarian Epithelial Cancer Small Intestine Lymphoma Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Recurrent Squamous Cell Carcinoma of the Hypopharynx Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Oropharynx HER2-negative Breast Cancer Stage IV Ovarian Germ Cell Tumor Unresectable Extrahepatic Bile Duct Cancer Unresectable Gallbladder Cancer Recurrent Extrahepatic Bile Duct Cancer Recurrent Gallbladder 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 Triple-negative Breast Cancer Advanced Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer Stage IV Pancreatic Cancer Stage IVA Cervical Cancer Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Salivary Gland Cancer Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Ovarian Stromal Cancer Recurrent Cervical Cancer Recurrent Endometrial Carcinoma Stage IV Endometrial Carcinoma Stage IVB Cervical Cancer Recurrent Esophageal Cancer Stage IV Esophageal Cancer Metastatic Gastrointestinal Carcinoid Tumor Recurrent Gastrointestinal Carcinoid Tumor Recurrent Adenoid Cystic Carcinoma of the Oral Cavity Recurrent Basal Cell Carcinoma of the Lip Recurrent Lymphoepithelioma of the Nasopharynx Recurrent Lymphoepithelioma of the Oropharynx Recurrent Mucoepidermoid Carcinoma of the Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Verrucous Carcinoma of the Larynx Recurrent Verrucous Carcinoma of the Oral Cavity Stage IV Adenoid Cystic Carcinoma of the Oral Cavity Stage IV Basal Cell Carcinoma of the Lip Stage IV Lymphoepithelioma of the Nasopharynx Stage IV Lymphoepithelioma of the Oropharynx Stage IV Mucoepidermoid Carcinoma of the Oral Cavity Stage IV Salivary Gland Cancer Stage IV Verrucous Carcinoma of the Larynx Stage IV Verrucous Carcinoma of the Oral Cavity Recurrent Gastric Cancer Stage IV Gastric Cancer Untreated Metastatic Squamous Neck Cancer With Occult Primary Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor Small Intestine Leiomyosarcoma Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Recurrent Anal Cancer Recurrent Small Intestine Cancer Small Intestine Adenocarcinoma Stage IV Anal Cancer Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
NCTId: NCT00031681

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)

Summary

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.

Detailed Description

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.

Eligibility

Eligibility Criteria

Gender Minimum Age Maximum Age Healthy Volunteers?
Both 18 Years N/A False

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

Interventions & Outcomes

Study Interventions & Types

Drug Intervention(s)

7-hydroxystaurosporine
7-hydroxystaurosporine
7-hydroxystaurosporine - Given IV
irinotecan hydrochloride - Given IV
irinotecan hydrochloride
irinotecan hydrochloride

Other Intervention(s)

diagnostic laboratory biomarker analysis - Correlative studies
laboratory biomarker analysis
laboratory biomarker analysis

Study Outcomes

Primary Outcome(s)

Timeframe: Every 6 weeks
Measure: 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)
Description: 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.
Safety Issue? No

Timeframe: Part I
Measure: DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
Safety Issue? Yes

Timeframe: Part I
Measure: MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
Description: Defined as the highest dose given to at least 6 patients in which =< 1 out of 6 experience dose limiting toxicity (DLT).
Safety Issue? Yes

Timeframe: Continuously over study treatment
Measure: Side effect profile of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in triple negative recurrent breast cancer (Part II)
Description: 95 % confidence interval will be calculated.
Safety Issue? No

Timeframe: Continuously over study treatment
Measure: Toxicities associated with irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I)
Description: Graded using the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Safety Issue? Yes

Secondary Outcome(s)

Measure: Anti-tumor activity of the combination of irinotecan hydrochloride and 7-hydroxystaurosporine in treatment of patients with resistant solid tumor malignancies
Timeframe: Every 6 weeks
Description: Evaluated by the RECIST criteria.
Safety Issue? No

Measure: In vivo mechanistic basis for 7-hydroxystaurosporine activity
Timeframe: Weekly during the first 4 weeks of course 1
Description: Explored by subgroup analysis (responders versus non-responders) on pharmacodynamic measures.
Safety Issue? No

Measure: Pharmacokinetics of irinotecan hydrochloride and 7-hydroxystaurosporine when administered in combination
Timeframe: Weekly during the first 4 weeks of course 1
Description: Using the high-performance liquid chromatography (HPLC) assays.
Safety Issue? No

Measure: Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations
Timeframe: Weekly during the first 4 weeks of course 1
Safety Issue? No

Facility Locations

Research Study Facility Map

Map of facility locations for this research study.

Facility is recruiting
Facility is not yet recruiting
Unknown status

Clinical Research Study Facility Locations

University of Virginia
Charlottesville, Virginia 22908 United States

Related Keywords & Studies

Conditions and Diseases with Related Research Studies

  1. Cancer
  2. Unspecified Adult Solid Tumor, Protocol Specific
  3. Estrogen Receptor-negative Breast Cancer
  4. Progesterone Receptor-negative Breast Cancer
  5. Stage IV Breast Cancer
  6. Recurrent Breast Cancer
  7. Stage IV Colon Cancer
  8. Recurrent Colon Cancer
  9. Stage IV Prostate Cancer
  10. Recurrent Prostate Cancer
  11. Gastrointestinal Stromal Tumor
  12. Carcinoma of the Appendix
  13. Extensive Stage Small Cell Lung Cancer
  14. Recurrent Pancreatic Cancer
  15. Recurrent Rectal Cancer
  16. Stage IV Rectal Cancer
  17. Stage IV Non-Small Cell Lung Cancer
  18. Recurrent Small Cell Lung Cancer
  19. Recurrent Non-Small Cell Lung Cancer
  20. Ovarian Sarcoma
  21. Recurrent Ovarian Epithelial Cancer
  22. Recurrent Ovarian Germ Cell Tumor
  23. Stage IV Ovarian Epithelial Cancer
  24. Small Intestine Lymphoma
  25. Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  26. Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  27. Recurrent Squamous Cell Carcinoma of the Hypopharynx
  28. Recurrent Squamous Cell Carcinoma of the Larynx
  29. Recurrent Squamous Cell Carcinoma of the Oropharynx
  30. HER2-negative Breast Cancer
  31. Stage IV Ovarian Germ Cell Tumor
  32. Unresectable Extrahepatic Bile Duct Cancer
  33. Unresectable Gallbladder Cancer
  34. Recurrent Extrahepatic Bile Duct Cancer
  35. Recurrent Gallbladder Cancer
  36. Stage IV Squamous Cell Carcinoma of the Hypopharynx
  37. Stage IV Squamous Cell Carcinoma of the Larynx
  38. Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
  39. Stage IV Squamous Cell Carcinoma of the Nasopharynx
  40. Stage IV Squamous Cell Carcinoma of the Oropharynx
  41. Triple-negative Breast Cancer
  42. Advanced Adult Primary Liver Cancer
  43. Recurrent Adult Primary Liver Cancer
  44. Stage IV Pancreatic Cancer
  45. Stage IVA Cervical Cancer
  46. Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  47. Recurrent Salivary Gland Cancer
  48. Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  49. Ovarian Stromal Cancer
  50. Recurrent Cervical Cancer
  51. Recurrent Endometrial Carcinoma
  52. Stage IV Endometrial Carcinoma
  53. Stage IVB Cervical Cancer
  54. Recurrent Esophageal Cancer
  55. Stage IV Esophageal Cancer
  56. Metastatic Gastrointestinal Carcinoid Tumor
  57. Recurrent Gastrointestinal Carcinoid Tumor
  58. Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
  59. Recurrent Basal Cell Carcinoma of the Lip
  60. Recurrent Lymphoepithelioma of the Nasopharynx
  61. Recurrent Lymphoepithelioma of the Oropharynx
  62. Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
  63. Recurrent Squamous Cell Carcinoma of the Nasopharynx
  64. Recurrent Verrucous Carcinoma of the Larynx
  65. Recurrent Verrucous Carcinoma of the Oral Cavity
  66. Stage IV Adenoid Cystic Carcinoma of the Oral Cavity
  67. Stage IV Basal Cell Carcinoma of the Lip
  68. Stage IV Lymphoepithelioma of the Nasopharynx
  69. Stage IV Lymphoepithelioma of the Oropharynx
  70. Stage IV Mucoepidermoid Carcinoma of the Oral Cavity
  71. Stage IV Salivary Gland Cancer
  72. Stage IV Verrucous Carcinoma of the Larynx
  73. Stage IV Verrucous Carcinoma of the Oral Cavity
  74. Recurrent Gastric Cancer
  75. Stage IV Gastric Cancer
  76. Untreated Metastatic Squamous Neck Cancer With Occult Primary
  77. Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
  78. Small Intestine Leiomyosarcoma
  79. Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  80. Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  81. Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
  82. Recurrent Anal Cancer
  83. Recurrent Small Intestine Cancer
  84. Small Intestine Adenocarcinoma
  85. Stage IV Anal Cancer
  86. Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor
  87. Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
  88. Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
  89. Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity

Other Related Condition Keywords

  1. Neoplasms
  2. Breast Neoplasms
  3. Colonic Neoplasms
  4. Lymphoma
  5. Sarcoma
  6. Esophageal Diseases
  7. Anus Neoplasms
  8. Papilloma
  9. Laryngeal Neoplasms
  10. Adenoma
  11. Pancreatic Neoplasms
  12. Carcinoma
  13. Prostatic Neoplasms
  14. Ovarian Neoplasms
  15. Granuloma
  16. Stomach Neoplasms
  17. Adenocarcinoma
  18. Gastrointestinal Neoplasms
  19. Carcinoma, Squamous Cell
  20. Head and Neck Neoplasms
  21. Carcinoma, Non-Small-Cell Lung
  22. Lung Neoplasms
  23. Laryngeal Diseases
  24. Liver Neoplasms
  25. Esophageal Neoplasms
  26. Endometrial Neoplasms
  27. Carcinoid Tumor
  28. Malignant Carcinoid Syndrome
  29. Neoplasms, Germ Cell and Embryonal
  30. Neoplasms, Glandular and Epithelial
  31. Uterine Cervical Neoplasms
  32. Neoplasms, Unknown Primary
  33. Rectal Neoplasms
  34. Salivary Gland Neoplasms
  35. Duodenal Neoplasms
  36. Ileal Neoplasms
  37. Jejunal Neoplasms
  38. Intestinal Neoplasms
  39. Small Cell Lung Carcinoma
  40. Carcinoma, Basal Cell
  41. Nasopharyngeal Neoplasms
  42. Gallbladder Neoplasms
  43. Leiomyosarcoma
  44. Bile Duct Neoplasms
  45. Oropharyngeal Neoplasms
  46. Gastrointestinal Stromal Tumors
  47. Carcinoma, Adenoid Cystic
  48. Germinoma
  49. Hypopharyngeal Neoplasms
  50. Paranasal Sinus Neoplasms
  51. Carcinoma, Verrucous
  52. Carcinoma, Mucoepidermoid
  53. Adenocarcinoma, Mucinous
  54. Esthesioneuroblastoma, Olfactory
  55. Papilloma, Inverted

Related Intervention Keywords

  1. <7-hydroxystaurosporine

Related Cancer Research

  1. (1)H-Nuclear Magnetic Resonance Spectroscopic Imaging of the Brain in Patients Who Receive Neurotoxic Therapy
  2. [F-18] Fluorothymidine (FLT) Imaging on Patients With Primary Brain Tumors
  3. 102 Annual Pap Smear Screening Database Maintenance Project
  4. 18F-NaF PET in Detecting Metastatic Bone Lesion for Patients With Cancer.
  5. 5-aza-2-deoxycytidine With Pegylated Interferon-alfa 2B: A Phase I Study With Molecular Correlates
  6. A Clinical Controlled Trial on the Effect of Physical Activity After Cancer Treatment (PACT)
  7. A Clinical Pharmacological Study of YM155 After Intravenous Infusion in Patients With Advanced Cancer
  8. A Clinical Study in Cancer Patients to Investigate the Potential Impact of Custirsen, on the Blood Levels of the Chemotherapeutic Drug, Paclitaxel, When Given Together as Part of a Treatment Regimen
  9. A Comparison of MBSR and CBT for the Treatment of Insomnia in Cancer
  10. A Dose Escalation Study of E7107 Administered Intravenously on Days 1 and 8 Every 21 Days to Patients With Solid Tumors