Irinotecan and Thalidomide in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with irinotecan may kill more tumor cells. This randomized phase I trial is studying the side effects and best way to give irinotecan and thalidomide in treating patients with metastatic or unresectable solid tumors

Detailed Description
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PRIMARY OBJECTIVES: I. Determine whether thalidomide alters the pharmacokinetics of irinotecan in patients with advanced solid tumors. II. Determine whether irinotecan alters the pharmacokinetics of thalidomide in these patients. III. Determine the toxicity of this regimen in these patients. IV. Determine the observed antitumor response in patients treated with this regimen. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irinotecan IV over 90 minutes on days 1 and 22 and oral thalidomide once daily on days 15-28. Arm II: Patients receive irinotecan as in arm I and oral thalidomide once daily on days -6 to 7. All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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A Phase I Pharmacokinetic Interaction Study of Irinotecan (NSC616348) and Thalidomide (NSC66847) in Patients With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: irinotecan hydrochloride
* Drug: thalidomide
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed malignant solid tumor Metastatic or unresectable Standard curative or palliative therapy is no longer effective or does not exist Measurable or assessable disease No uncontrolled brain metastases Patients with brain metastases are eligible provided the following are true: Stable neurologic status At least 4 weeks since prior steroids or anticonvulsants No neurologic dysfunction that would confound evaluation Performance status - Karnofsky 70-100% More than 12 weeks WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No history of inflammatory bowel disease requiring therapy No chronic diarrhea syndromes No paralytic ileus Not pregnant or nursing Negative pregnancy test Fertile female patients must use 2 forms of effective contraception, including 1 highly effective method, for at least 4 weeks before, during, and for 4 weeks after study participation Male patients must use effective barrier contraception during and for 4 weeks after study participation No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs No uncontrolled seizure disorder No other concurrent uncontrolled illness that would preclude study participation No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection No significant traumatic injury within the past 28 days No serious, nonhealing wounds or ulcers No bone fractures No preexisting peripheral neuropathy grade 2 or greater At least 4 weeks since prior biologic therapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) See Disease Characteristics At least 4 weeks since prior radiotherapy More than 28 days since prior major surgical procedure or open biopsy At least 4 weeks since prior investigational therapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational or commercial agents or therapies for the malignancy

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (irinotecan hydrochloride and thalidomide)<br>Patients receive irinotecan IV over 90 minutes on days 1 and 22 and oral thalidomide once daily on days 15-28. All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: irinotecan hydrochloride<br>* Given IV<br>* Other names: U-101440E;Drug: thalidomide<br>* Given orally<br>* Other names: Thalomid;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|
| Experimental: Arm II (irinotecan hydrochloride and thalidomide)<br>Patients receive irinotecan as in arm I and oral thalidomide once daily on days -6 to 7. All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: irinotecan hydrochloride<br>* Given IV<br>* Other names: U-101440E;Drug: thalidomide<br>* Given orally<br>* Other names: Thalomid;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of thalidomide on irinotecan hydrochloride pharmacokinetics |  | Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 hours | 
| Effect of irinotecan hydrochloride on thalidomide pharmacokinetics |  | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 and 24 and 168 hours | 
| Grade 3 or greater toxicities assessed using NCI CTC version 2.0 | Will be summarized and analyzed using descriptive statistics. Exact 90% confidence intervals using the binomial distribution will be derived. | Up to 3 years | 
| Response assessed using RECIST criteria | Will be summarized and analyzed using descriptive statistics. Exact 90% confidence intervals using the binomial distribution will be derived. | Up to 3 years |