Irinotecan Plus Gemcitabine in Treating Patients With Unresectable or Metastatic Solid Tumors

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT00004095

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

110

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 and gemcitabine in treating patients who have unresectable or metastatic solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Breast Cancer Colorectal Cancer Kidney Cancer Lung Cancer Pancreatic Cancer	Drug: gemcitabine hydrochloride Drug: irinotecan hydrochloride	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose (MTD) and the principal toxicities of irinotecan and gemcitabine in patients with surgically unresectable or metastatic solid tumors.
Determine if the principal toxicities and MTD of this combination regimen are affected by drug sequencing in this patient population.
Determine the potential for gemcitabine to alter the pharmacokinetic characteristics when administered with irinotecan in these patients.
Describe the influence effected by varying the administration sequence of this combination regimen in this patient population.
Obtain preliminary data regarding efficacy of this combination regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive irinotecan IV over 90 minutes followed by gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) is reached, patients receive subsequent doses of the inverse sequence of the combination drugs until a new MTD is determined.

Cohorts of 3-6 patients receive escalating doses of irinotecan and gemcitabine until the MTD is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months until death.

PROJECTED ACCRUAL: At least 12 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Trial of Irinotecan (CPT-11) and Gemcitabine in Patients With Solid Tumors

Study Start Date :

Aug 1, 1999

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Irinotecan Plus Gemcitabine	Drug: gemcitabine hydrochloride Drug: irinotecan hydrochloride

Arm

Intervention/Treatment

Experimental: Irinotecan Plus Gemcitabine

Drug: gemcitabine hydrochloride

Drug: irinotecan hydrochloride

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic or surgically unresectable solid tumor, having received the following maximum number of prior therapies for advanced disease:
Bladder cancer - no more than 1 prior therapy
Breast cancer - no more than 2 prior therapies
Colorectal cancer - no more than 1 prior therapy
Kidney cancer - no prior therapy
Lung cancer - no more than 1 prior therapy
Pancreatic cancer - no prior therapy
Bidimensionally measurable disease outside a previously irradiated field
At least 2 cm x 2 cm
No known bone metastases
CNS involvement allowed if successfully controlled by surgery or radiotherapy and not requiring corticosteroids
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Menopausal status:

Not specified

Performance status:

ECOG 0-2

Life expectancy:

At least 3 months

Hematopoietic:

Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 mg/dL regardless of liver involvement secondary to tumor
SGOT no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN if liver metastases present)
No known Gilbert's disease

Renal:

Creatinine no greater than 1.8 mg/dL
Calcium less than 12.0 mg/dL

Cardiovascular:

No myocardial infarction within the past 6 months
No congestive heart failure requiring therapy

Other:

No active uncontrolled bacterial, viral (including HIV), or invasive fungal infection
No psychiatric disorders that would prevent compliance
No other malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
No history of seizures
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent sargramostim (GM-CSF)
No concurrent immunotherapy

Chemotherapy:

No prior irinotecan, topotecan, or gemcitabine
Prior adjuvant chemotherapy allowed, if at least 1 year between last dose of adjuvant chemotherapy and recurrence of cancer
No other concurrent chemotherapy