UCN-01 and Cisplatin in Treating Patients With Advanced or Metastatic Solid Tumors

Phase I Dose Escalation Study of UCN-01 (NSC 638850) Plus Cisplatin in Advanced Malignant Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of UCN-01 and cisplatin in treating patients who have advanced or metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: cisplatin; Drug: 7-hydroxystaurosporine

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of cisplatin when administered with UCN-01 in patients with advanced solid tumors.
• Assess the toxicity and potential antitumor activity of this regimen in these patients.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study of cisplatin.

Patients receive cisplatin IV over 1 hour on day 1 and UCN-01 IV continuously over 36-72 hours beginning on day 2. Treatment continues every 4 weeks for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of cisplatin 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.

Patients are followed every 2-3 months for at least 1 year.

PROJECTED ACCRUAL: A total of 9-30 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Pasadena, California, United States, 91105
      • City of Hope Medical Group
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced or metastatic solid tumor incurable by surgery or other standard therapy
• Tumor site accessible by biopsy
• No brain metastasis

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 4,500/mm3
• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 150,000/mm3

Hepatic:

• Bilirubin normal
• SGOT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV congestive heart failure

Other:

• No peripheral neuropathy greater than grade I
• No history of allergic reactions to diuretics or antiemetics (e.g., 5-HT3 antagonists) that would preclude study
• No other uncontrolled illness that would preclude study, including intolerance to vigorous hydration
• No medical, social, or psychological factors that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• No greater than 2 prior chemotherapy regimens
• Prior cisplatin allowed if cumulative dose no greater than 400 mg/m2

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• Recovered from any prior surgery

Other:

• At least 30 days since prior investigational drugs
• No other concurrent investigational drugs
• No other concurrent anticancer agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David R. Gandara, MD, University of California, Davis

Publications and helpful links

General Publications

• Lara PN Jr, Mack PC, Synold T, Frankel P, Longmate J, Gumerlock PH, Doroshow JH, Gandara DR. The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial. Clin Cancer Res. 2005 Jun 15;11(12):4444-50. doi: 10.1158/1078-0432.CCR-04-2602.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: November 6, 2000
• First Submitted That Met QC Criteria: May 29, 2003
• First Posted (Estimate): May 30, 2003

Study Record Updates

• Last Update Posted (Estimate): January 15, 2010
• Last Update Submitted That Met QC Criteria: January 13, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; 7-hydroxystaurosporine
• Other Study ID Numbers: CDR0000068274; P30CA033572 (U.S. NIH Grant/Contract); U01CA062505 (U.S. NIH Grant/Contract); CHNMC-PHI-28; NCI-T99-0065