Clinical trial NCT00896454: Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium
Official title: A Single-arm, Multicenter, Proof-of-concept Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium Despite Recent Treatment With IV Bisphosphonates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Hypercalcemia of Malignancy
Colon Cancer
Endocrine Cancer
Head and Neck Cancer
Kidney Cancer
Lung Cancer
Lymphoma
Metastatic Cancer
Multiple Myeloma
Parathyroid Neoplasms
Renal Cancer
Thyroid Cancer
Hodgkin's Lymphoma
Non-Hodgkin's Lymphoma
Non-Small Cell Lung Cancer
Keywords: hypercalcemia
calcium
bisphosphonates
denosumab
amgen
malignancy
20070315
HMC
oncology
hematology
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2009-05-11
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the potential of denosumab to treat Hypercalcemia of Malignancy in patients with elevated serum calcium who do not respond to recent treatment with intravenous bisphosphonates by lowering corrected serum calcium \</= 11.5 mg/dL (2.9 millimoles /L) by day 10.


Eligibility criteria: Inclusion Criteria:

* Hypercalcemia of Malignancy (HCM) as defined as documented histologically or cytologically confirmed cancer and a corrected serum calcium (CSC) \> 12.5 mg/dL (3.1 millimoles /L) at screening by local laboratory
* Last IV bisphosphonate treatment must be \>/= to 7 days and \</= to 30 days before the screening corrected serum calcium
* Adults (\>/=18 years)
* Adequate organ function as defined by the following criteria:
* serum aspartate aminotransferase (AST) \</= 5 x upper limit of normal (ULN)
* serum alanine aminotransferase (ALT) \</= 5 x upper limit of normal
* serum total bilirubin \</= 2 x upper limit of normal

Exclusion Criteria:

* Evidence of benign hyperparathyroidism, hyperthyroidism, adrenal insufficiency, vitamin D intoxication, milk alkali syndrome, sarcoidosis, or other granulomatous disease
* Receiving dialysis for renal failure
* Treatment with thiazides, calcitonin, mithramycin, or gallium nitrate within their window of expected therapeutic effect (as determined by the physician) prior to the date of the screening CSC
* Treatment with cinacalcet within 4 weeks prior to the date of the screening CSC
* Thirty days or less since receiving an investigational product (other than denosumab) or device (ie, does not have marketing authorization; thalidomide use is allowed) in another clinical study
* Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products)
* Female subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
* Female subject of childbearing potential is not willing to use 2 highly effective methods of contraception during treatment and for 7 months after the end of treatment
* Subject will not be available for follow-up assessment.
* Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results

Primary outcomes:
measure: Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab
timeFrame: 10 days
Secondary outcomes:
measure: Percentage of Participants With a Response by Visit
timeFrame: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
measure: Percentage of Participants With a Complete Response by Visit
timeFrame: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
measure: Time to Response
timeFrame: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.
measure: Time to Complete Response
timeFrame: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.
measure: Duration of Response
timeFrame: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.
measure: Duration of Complete Response
timeFrame: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.
measure: Time to Relapse/Nonresponse of Hypercalcemia of Malignancy
timeFrame: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.
measure: Change From Baseline in Corrected Serum Calcium
timeFrame: Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Salisbury
country: United States
facility: Research Site
state: Maryland
city: Dearborn
country: United States
facility: Research Site
state: Michigan
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Bronx
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Syracuse
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Goldsboro
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: QuÃ©bec
country: Canada
facility: Research Site
state: Quebec
city: Québec
country: Canada
facility: Research Site
state: Quebec
city: Limoges Cedex
country: France
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Villejuif cedex
country: France
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Hu MI, Glezerman I, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Ying W, Jain RK. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment. J Natl Cancer Inst. 2013 Sep 18;105(18):1417-20. doi: 10.1093/jnci/djt225. Epub 2013 Aug 29.