A Phase I Pharmacokinetic Interaction Study of Irinotecan (NSC616348) and Thalidomide (NSC66847) in Patients With Advanced Solid Tumors
A Phase I Pharmacokinetic Interaction Study of Irinotecan (NSC616348) and Thalidomide (NSC66847) in Patients With Advanced Solid Tumors
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
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.
Inclusion Criteria:
Histologically confirmed malignant solid tumor
Measurable or assessable disease
No uncontrolled brain metastases
Patients with brain metastases are eligible provided the following are true:
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