Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Thyroid Neoplasms

Thyroid Diseases

Head and Neck Neoplasms

Carcinoma, Renal Cell

Neoplasm Metastasis

Lung Neoplasms

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hodgkin Disease

Kidney Neoplasms

Parathyroid Neoplasms

Hypercalcemia

Syndrome

Paraneoplastic Syndromes

Endocrine Gland Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Endocrine System Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Metabolic Diseases

Calcium Metabolism Disorders

Water-Electrolyte Imbalance

Parathyroid Diseases

Renal Cell Carcinoma

Lymphosarcoma

Hodgkin Lymphoma

All Drugs and Chemicals

Bone Density Conservation Agents

Calcium

Calcium, Dietary

Denosumab

Diphosphonates

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.

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

denosumab

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.

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

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

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 \[g/dL\]))

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 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 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 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 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 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.

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Participants received 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.

Denosumab 120 mg Q4W

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Other

Race/Ethnicity, Customized

Scale used to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about \> 50% of waking hours; 3 = Capable of only limited self care, confined to a bed or chair \> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Bladder

Breast

Head and neck

Liver

Neuroendocrine/carcinoid

Non-hodgkin's

Non-small cell lung cancer

Ovarian

Renal

Small cell lung cancer

Soft tissue sarcoma

Unknown (primary tumor)

Multiple myeloma

Chronic lymphocytic leukemia

IGG kappa multiple myeloma

Myeloma

Primary Tumor Type

Time from initial cancer diagnosis to enrollment

Presence of metastatic disease at enrollment

Presence of bone metastatic disease at enrollment

Fatigue

Anorexia

Nausea

Depressed level of consciousness

Vomiting

Dry mouth

Constipation

Lethargy

Confusion

Polyuria

Abdominal pain

Decreased mental acuity

Dyspnea

General weakness

Insomnolence

Light headedness (dizziness)

Listlessness/muscle weakness

Polyuro-polydipsic syndrome

Psychomotor retardation

Retching

Urinary frequency

Weight loss

Participants may have had more than one symptom

Baseline Hypercalcemia of Malignancy (HCM) Symptoms

Calcium (corrected)

Study Director

Response Analysis Subset including all participants who received at least 1 dose of denosumab and had a screening CSC (from local lab) \> 12.5 mg/dL (3.1 mmol/L).

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

By Day 2

By Day 4

By Day 8

By Day 10

By Day 15

By Day 19

By Day 23

By Day 29

By Day 36

By Day 43

By Day 50

By Day 57

Percentage of Participants With a Response by Visit

Percentage of Participants With a Complete Response by Visit

Time to Response

Time to Complete Response

Participants with a response in the Response Analysis Subset

Duration of Response

Participants with a complete response in the Response Analysis Subset

Duration of Complete Response

Time to Relapse/Nonresponse of Hypercalcemia of Malignancy

Change from Baseline to Day 2 (n = 32)

Change from Baseline to Day 4 (n = 32)

Change form Baseline to Day 8 (n = 27)

Change from Baseline to Day 10 (n = 28)

Change from Baseline to Day 15 (n = 24)

Change from Baseline to Day 19 (n = 22)

Change from Baseline to Day 23 (n = 21)

Change from Baseline to Day 29 (n = 22)

Change from Baseline to Day 36 (n = 20)

Change from Baseline to Day 43 (n = 19)

Change from Baseline to Day 50 (n = 15)

Change from Baseline to Day 57 (n = 17)

Efficacy Analysis Subset included all participants who received at least 1 dose of denosumab. n = Number of participants who had non-missing data at Baseline and the time point of interest.

Change From Baseline in Corrected Serum Calcium

Overall Study

Spots Global Cancer Trial Database for Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial