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”

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.

Intervention(s) in this Clinical Trial

• Drug: denosumab
  • 120 mg subcutaneously (SC) every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: denosumab
  • Eligible subjects will receive denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study days 8 and 15.

Primary Measures

• Proportion of subjects with a response, defined as corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) within 10 days after the first dose of denosumab.
  • Time Frame: 10 days
    Safety Issue?: No

Secondary Measures

• Proportion of subjects with a response (ie, corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) by visit
  • Time Frame: 33 months
    Safety Issue?: No
• Proportion of subjects with a complete response (CR) (ie, corrected serum calcium </= 10.8 mg/dL (2.7 millimoles/L) by visit
  • Time Frame: 33 months
    Safety Issue?: No
• Time to response
  • Time Frame: 33 months
    Safety Issue?: No
• Time to complete response
  • Time Frame: 33 months
    Safety Issue?: No
• Duration of response defined as the number of days from the first day of corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L) to the last day of corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L)
  • Time Frame: 33 months
    Safety Issue?: No
• Time to relapse/nonresponse of hypercalcemia of malignancy defined as the number of days from the day of the first dose of denosumab until the last day of corrected serum calcium </= 11.5 mg/dL (2.9 millimoles/L)
  • Time Frame: 33 months
    Safety Issue?: No
• Changes in corrected serum calcium from baseline
  • Time Frame: 33 months
    Safety Issue?: No
• Duration of complete response defined as the number of days from the first day of of corrected serum calcium </= 10.8 mg/dL (2.7 millimoles/L) to the last day of corrected serum calcium </= 10.8 mg/dL (2.7 millimoles/L)
  • Time Frame: 33 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Amgen Industry

Overall Clinical Trial Officials and Contacts

MD Study Director Amgen  

Overall Contact: Amgen Call Center 866-572-6436 

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00896454

Study ID Number: 20070315

ClinicalTrials.gov Identifier: NCT00896454

Health Authority: United States: Food and Drug Administration

AmgenTrials clinical trials website