Clinical Trial: 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 Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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. Co
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • MTD of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I) [ Time Frame: Part I ]
    Defined as the highest dose given to at least 6 patients in which =< 1 out of 6 experience dose limiting toxicity (DLT).
  • DLT of irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I) [ Time Frame: Part I ]
  • Toxicities associated with irinotecan hydrochloride in combination with 7-hydroxystaurosporine in patients with resistant solid tumor malignancies (Part I) [ Time Frame: Continuously over study treatment ]
    Graded using the Cancer Therapy Evaluation Program (CTEP) Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
  • 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) [ Time Frame: Every 6 weeks ]
    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.
  • Side effect profile of 7-hydroxystaurosporine in combination with irinotecan hydrochloride in triple negative recurrent breast cancer (Part II) [ Time Frame: Continuously over study treatment ]
  • Anti-tumor activity of the combination of irinotecan hydrochloride and 7-hydroxystaurosporine in treatment of patients with resistant solid tumor malignancies [ Time Frame: Every 6 weeks ]
    Evaluated by the RECIST criteria.
  • Pharmacokinetics of irinotecan hydrochloride and 7-hydroxystaurosporine when administered in combination [ Time Frame: Weekly during the first 4 weeks of course 1 ]
    Using the high-performance liquid chromatography (HPLC) assays.
  • Serum alpha-acid glycoprotein and correlate this level with free 7-hydroxystaurosporine concentrations [ Time Frame: Weekly during the first 4 weeks of course 1 ]
  • In vivo mechanistic basis for 7-hydroxystaurosporine activity [ Time Frame: Weekly during the first 4 weeks of course 1 ]
    Explored by subgroup analysis (responders versus non-responders) on pharmacodynamic measures.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 8, 2002
Date Started: December 2001
Date Completion:
Last Updated: September 27, 2013
Last Verified: September 2013