Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00896454
First received: May 7, 2009
Last updated: December 19, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: denosumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))


Secondary Outcome Measures:
  • Percentage of Participants With a Response by Visit [ Time Frame: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57 ] [ Designated as safety issue: No ]
    Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL]))

  • Percentage of Participants With a Complete Response by Visit [ Time Frame: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57 ] [ Designated as safety issue: No ]
    Response is defined as corrected serum calcium (CSC) ≤ 10.8 mg/dL (2.7 mmol/L). For all CSC values, if albumin was < 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium [mg/dL] + (0.8 x (4 - serum albumin [g/dL])).

  • Time to Response [ Time Frame: 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. ] [ Designated as safety issue: No ]

    Time to Response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if no response was observed. If there was no post-baseline CSC assessment, time to response was censored on study Day 1.

    Time to response was analyzed using Kaplan-Meier methods.


  • Time to Complete Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Time to complete response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) was ≤ 10.8 mg/dL (2.7 mmol/L). Participants were censored on the last CSC assessment day if no complete response was observed. If there was no post-baseline CSC assessment, time to complete response was censored on study Day 1. Time to complete response was analyzed using Kaplan-Meier methods.

  • Duration of Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Duration of response is 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. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after the first response. If a participant had no CSC assessment after the first response, duration of response was set to zero and censored. Duration of response was summarized for participants who achieved a response using the Kaplan-Meier method.

  • Duration of Complete Response [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Duration of complete response is 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. Participants were censored on the last CSC assessment day if their CSC level never reached > 10.8 mg/dL after the complete response. If a participant had no CSC assessment after the complete response, duration of complete response was set to zero and censored. Duration of complete response was summarized for participants who achieved a complete response using the Kaplan-Meier method.

  • Time to Relapse/Nonresponse of Hypercalcemia of Malignancy [ Time Frame: 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. ] [ Designated as safety issue: No ]
    Time to relapse/nonresponse was defined as the number of days from study Day 1 until the last day of CSC ≤ 11.5 mg/dL for all particiipants with relapse after the first response. Participants were censored on the last CSC assessment day if their CSC level never reached > 11.5 mg/dL after first response. For participants who never achieved response, time to relapse/nonresponse was set to zero. Otherwise, if there was no post-baseline CSC assessment, time to relapse/nonresponse was censored on study Day 1. Time to relapse/nonresponse was estimated using the Kaplan-Meier method.

  • Change From Baseline in Corrected Serum Calcium [ Time Frame: Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57 ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: November 2009
Study Completion Date: October 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: denosumab
120 mg subcutaneously (SC) every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896454

Locations
United States, California
Research Site
Encinitas, California, United States, 92024
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06520
United States, Maryland
Research Site
Salisbury, Maryland, United States, 21801
United States, Michigan
Research Site
Dearborn, Michigan, United States, 48124
Research Site
Detroit, Michigan, United States, 48236
United States, Nebraska
Research Site
Omaha, Nebraska, United States, 68114
United States, New York
Research Site
Bronx, New York, United States, 10467
Research Site
New York, New York, United States, 10065
Research Site
Syracuse, New York, United States, 13210
United States, North Carolina
Research Site
Durham, North Carolina, United States, 27710
Research Site
Goldsboro, North Carolina, United States, 27534
United States, Texas
Research Site
Houston, Texas, United States, 77030
Canada, Quebec
Research Site
Québec, Quebec, Canada, G1S 4L8
Research Site
Québec, Quebec, Canada, G1S 4L8
France
Research Site
Limoges Cedex, France, 87042
Research Site
Montpellier Cedex 5, France, 34298
Research Site
Nantes Cedex 1, France, 44035
Research Site
Villejuif cedex, France, 94805
Italy
Research Site
Bologna, Italy, 40138
Research Site
Firenze, Italy, 50139
Research Site
Milano, Italy, 20162
Research Site
Padova, Italy, 35128
Research Site
Roma, Italy, 00128
Poland
Research Site
Warszawa, Poland, 01-809
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00896454     History of Changes
Other Study ID Numbers: 20070315
Study First Received: May 7, 2009
Results First Received: December 19, 2014
Last Updated: December 19, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Amgen:
hypercalcemia
calcium
bisphosphonates
denosumab
amgen
malignancy
20070315
HMC
oncology
hematology

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Head and Neck Neoplasms
Hodgkin Disease
Hypercalcemia
Kidney Neoplasms
Lung Neoplasms
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasm Metastasis
Neoplasms
Paraneoplastic Syndromes
Parathyroid Neoplasms
Thyroid Neoplasms
Adenocarcinoma
Blood Protein Disorders
Bronchial Neoplasms
Calcium Metabolism Disorders
Carcinoma
Carcinoma, Bronchogenic
Cardiovascular Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Kidney Diseases

ClinicalTrials.gov processed this record on August 27, 2015