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NCT Number: NCT00896454

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

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.

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Key information

Conditions

Breast Cancer Blood Protein Disorders Breast Diseases Breast Neoplasms Bronchial Neoplasms Calcium Metabolism Disorders Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Cardiovascular Diseases Colon Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Cancer Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Cancer Head and Neck Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hodgkin Disease Hodgkin's Lymphoma Humoral Hypercalcemia Of Malignancy Hypercalcemia Hypercalcemia of Malignancy Immune System Diseases Immunoproliferative Disorders Intestinal Diseases Intestinal Neoplasms Kidney Cancer Kidney Diseases Kidney Neoplasms Lung Cancer Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Metabolic Diseases Metastatic Cancer Multiple Myeloma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Neoplastic Processes Non-Hodgkin's Lymphoma Non-small Cell Lung Cancer Nutritional and Metabolic Diseases Paraproteinemias Parathyroid Diseases Parathyroid Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Thoracic Neoplasms Thyroid Cancer Thyroid Diseases Thyroid Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Vascular Diseases Water-Electrolyte Imbalance

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Québec, Quebec, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Denosumab

Drug

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

Primary outcomes

  1. Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab

    Time frame: 10 days

    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 outcomes

  1. Percentage of Participants With a Response by Visit

    Time frame: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

    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]))

  2. 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

    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])).

  3. 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.

    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.

  4. 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.

    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.

  5. 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.

    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.

  6. 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.

    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.

  7. 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.

    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.

  8. 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

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2012
Study completion
2013
First posted
May 11, 2009
Registry last updated
Oct 17, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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