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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Bladder Cancer, Breast Cancer, Colorectal Cancer, Kidney Cancer, Lung Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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 Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy to less than 30% of bone marrow No prior whole pelvic radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics Other: No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan Plus Gemcitabine<br> | Drug: gemcitabine hydrochloride<br> <br> Drug: irinotecan hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IV pancreatic cancer, stage IV colon cancer, stage IV breast cancer, recurrent breast cancer, recurrent pancreatic cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, stage IV renal cell cancer, recurrent renal cell cancer, extensive stage small cell lung cancer, recurrent small cell lung cancer, recurrent bladder cancer, stage IV bladder cancer, stage IV non-small cell lung cancer