Irinotecan and Gemcitabine in Treating Patients With Refractory Advanced Solid Tumors

Escalating Irinotecan (CPT-11) Administered 24 Hours Prior To Gemcitabine In Patients With Refractory 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 combining irinotecan with gemcitabine in treating patients who have refractory advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: gemcitabine hydrochloride

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of irinotecan when administered with gemcitabine in patients with refractory advanced solid tumors.
• Determine the antitumor activity and toxicity of this regimen in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.
• Determine the optimal dose and time interval for this regimen in these patients.

OUTLINE: This is an open-label, non-randomized, dose-escalation study of irinotecan.

Patients receive irinotecan IV over 90 minutes on days 1 and 8 and gemcitabine IV over 30 minutes on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

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 solid tumor that is refractory to prior treatment

  • Considered incurable with other modalities

• Measurable or evaluable disease

  • The following are not considered measurable or evaluable:

    • Bone metastases
    • Pleural, pericardial, or peritoneal effusions
    • Irradiated lesions (unless progression is documented after radiotherapy)
  • Metastatic disease that has been followed using serum tumor markers allowed
• No symptomatic brain metastases
• Brain metastases may not be sole site of metastatic disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• AST and ALT no greater than 1.5 times normal
• Bilirubin no greater than 1.5 mg/dL
• No clinically apparent jaundice

Renal

• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular

• Cardiac function normal
• No uncontrolled heart disease
• No myocardial infarction within the past 3 months
• No congestive heart failure
• No unstable or uncontrolled angina

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active infection requiring systemic therapy
• No uncontrolled seizures
• No uncontrolled diabetes mellitus

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior gemcitabine
• No prior camptothecin compounds
• Prior irinotecan allowed
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 14 days since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 30 days since prior clinical trial participation
• No other concurrent investigational medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Study Chair: Nithya Ramnath, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): May 1, 2003
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): January 13, 2014
• Last Update Submitted That Met QC Criteria: January 10, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Irinotecan
• Other Study ID Numbers: CDR0000270343; RPCI-DS-01-18