Calcitriol and Gefitinib With or Without Dexamethasone in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Calcitriol may help tumor cells develop into normal cells. Dexamethasone may increase the effectiveness and decrease the side effects of gefitinib and calcitriol. PURPOSE: This phase I trial is studying the side effects and best dose of calcitriol when given together with gefitinib or when given together with gefitinib and dexamethasone in treating patients with advanced solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose (MTD), toxic effects, and tolerability of calcitriol alone and in combination with gefitinib with or without dexamethasone in patients with advanced solid tumors. Secondary Determine the pharmacokinetics and pharmacodynamics of these regimens in these patients. Determine any tumor responses in patients treated with these regimens. OUTLINE: This is a dose-escalation study of calcitriol. Stage 1: Patients receive calcitriol IV over 1 hour on days 1, 15, and 22 and oral gefitinib once daily on days 8-28 during course 1. For all subsequent courses, patients receive calcitriol IV over 1 hour on days 1, 8, 15, and 22 and oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of calcitriol with a fixed dose of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Stage 2: Patients receive calcitriol (beginning at 1 dose level below the MTD determined in stage 1) and gefitinib as in stage 1. Patients also receive oral dexamethasone once on the day before and twice on the day of each dose of calcitriol. Cohorts 3-6 patients receive escalating doses of calcitriol with fixed doses of gefitinib and dexamethasone until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 21-36 patients will be accrued for this study within 1 year.

Official Title
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A Phase I Study of Intravenous (IV) Calcitriol in Combination With ZD1839 (IRESSA®) in Refractory Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Dietary Supplement: calcitriol
* Drug: dexamethasone
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumor Metastatic or unresectable disease Standard curative or palliative measures do not exist or are no longer effective No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy More than 3 months Hematopoietic WBC ≥ 3,000/mm^3 Hemoglobin ≥ 8 g/dL Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal No unstable or uncompensated hepatic disease Renal Creatinine normal OR Creatinine clearance ≥ 60 mL/min No prior hypercalcemia No kidney, ureteral, or bladder stones within the past 10 years No unstable or uncompensated renal disease Cardiovascular Ejection fraction ≥ 30% No heart failure or significant heart disease No significant arrhythmias No myocardial infarction within the past 3 months No unstable angina pectoris No symptomatic congestive heart failure No other unstable or uncompensated cardiac disease Pulmonary No evidence of clinically active interstitial lung disease Chronic, stable, asymptomatic, radiographic changes allowed No other unstable or uncompensated respiratory disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 30 days after study treatment Able to receive oral medication Willing to have serial skin biopsies No prior allergic reaction to compounds of similar chemical or biological composition to study drugs or other agents used in this study No ongoing or active infection No known severe hypersensitivity to gefitinib or any of its excipients No psychiatric illness or social situation that would preclude study compliance No other severe or uncontrolled systemic disease or concurrent illness that would preclude study participation No other significant clinical disorder or laboratory finding that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Endocrine therapy No other concurrent systemic glucocorticoid therapy Radiotherapy More than 4 weeks since prior radiotherapy and recovered Surgery Recovered from prior major surgery No prior nephrectomy Other Recovered from all prior anticancer therapy More than 30 days since prior non-approved or investigational drugs More than 7 days since prior thiazides No concurrent administration of any of the following: Combination antiretroviral therapy for HIV-positive patients Phenytoin Carbamazepine Barbiturates Rifampin Phenobarbital Hypericum perforatum (St. John's wort) Calcium supplements Thiazides Digoxin No other concurrent investigational or commercial anticancer agents or therapies

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
Intervention Model: Single Group Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: calcitriol|nan|
|Drug: dexamethasone|nan|
|Drug: gefitinib|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific