Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Supportive care	Closed	over 18		MSKCC-90117 NCI-V90-0194

Objectives

I.  Assess the relative efficacy of and tolerance to a single dose of 
intravenous MK-217 compared to that of thrice daily etidronate in patients 
with malignancy-associated hypercalcemia.
II.  Determine the safety of and tolerance to 10 and 15 mg MK-217 infused 
intravenously over 4 and 12 hours, respectively, in these patients.
III.  Determine the duration of efficacy for both treatment regimens.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over 18 years of age with a 
histologically diagnosed malignancy that is considered the cause of 
hypercalcemia; hypercalcemia is defined as an albumin-corrected serum calcium 
of at least 11.5 mg/dl after intravenous hydration with at least 3 liters NS 
(at least 50 ml/kg if body weight is less than 60 kg) with a urinary output of 
1,500 ml over the previous 24 hours.  Patients with parathyroid carcinoma are 
ineligible, as are those with clinical or biochemical evidence of a cause of 
hypercalcemia other than malignancy (e.g., hyperparathyroidism, drug or 
exogenous vitamin-related hypercalcemia, hyperthyroidism, and sarcoidosis).  
At least 1 week must have elapsed since any antitumor therapy, and there must 
be no requirement for such therapy within 7 days after protocol treatment; 
planned treatment may begin after normocalcemia is demonstrated.  Patients on 
medical antitumor therapy (e.g., corticosteroids, high-dose estrogen, 
megestrol, and tamoxifen) at a stable dose for at least 2 weeks may continue 
such therapy at the same dose or, in the case of corticosteroids, at a 
decreased dose, and corticosteroids may be used for medical indications other 
than antitumor therapy.  Therapy specifically intended to reduce serum calcium 
(e.g., calcitonin, plicamycin, corticosteroids, gallium, phosphate) must not 
be initiated within the week prior to treatment, and at least 6 months must 
have elapsed since prior bisphosphonate therapy; a history of allergy, 
hypersensitivity, or intolerance to any bisphosphonate excludes.  
Administration of furosemide or other potent loop diuretic is not permitted in 
the 24 hours prior to entry.  Patients who have received drugs with 
established nephrotoxicity (e.g., aminoglycoside antibiotics, amphotericin B, 
and acyclovir) within 48 hours prior to entry are ineligible, as are those who 
have received any investigational drug within 30 days prior to treatment or 
who anticipate receiving such a drug within 30 days after treatment.  A life 
expectancy of at least 6 weeks is required, and there must be no evidence of 
major renal dysfunction (serum creatinine greater than 2.5 mg/dl) after 
initial hydration.  The following conditions exclude:  decompensated 
congestive heart failure; active upper gastrointestinal bleeding of any 
etiology; and fever within 24 hours of treatment.  Fertile women must have a 
negative pregnancy test, and nursing women are excluded.  Patients with 
evidence or a history of any illness that might confound the results of the 
study or pose additional risk from the study drugs are ineligible.

Expected Enrollment

120 patients will be entered on each arm of this multicenter study; accrual is 
expected to require 9 months to complete.

Outline

Randomized, double-blind study.
Arm I:  Antihypercalcemia Therapy.  MK-217.
Arm II:  Antihypercalcemia Therapy.  Etidronate.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Raymond Warrell, MD, Protocol chair(Contact information may not be current)		Ph: 212-639-8168; 800-525-2225