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


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Safety Issue:

Yes

Principal Investigator

Marwan Fakih, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000365546

NCT ID:

NCT00084708

Start Date:

November 2002

Completion Date:

May 2007

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263