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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00896454
• Other study ID #: 20070315
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2009
• Est. completion date: August 21, 2013

Study information

• Verified date: September 2018
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: August 21, 2013
• Est. primary completion date: September 13, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Colon Cancer
• Endocrine Cancer
• Endocrine Gland Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Hodgkin Disease
• Hodgkin's Lymphoma
• Hypercalcemia
• Hypercalcemia of Malignancy
• Kidney Cancer
• Kidney Neoplasms
• Lung Cancer
• Lung Neoplasms
• Lymphoma
• Lymphoma, Non-Hodgkin
• Metastatic Cancer
• Multiple Myeloma
• Neoplasm Metastasis
• Neoplasms
• Non-Hodgkin's Lymphoma
• Non-Small Cell Lung Cancer
• Paraneoplastic Syndromes
• Parathyroid Neoplasms
• Renal Cancer
• Thyroid Cancer
• Thyroid Neoplasms

Intervention

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

Locations

Country	Name	City	State
Canada	Research Site	Québec	Quebec
Canada	Research Site	Québec	Quebec
France	Research Site	Limoges Cedex
France	Research Site	Montpellier Cedex 5
France	Research Site	Nantes Cedex 1
France	Research Site	Villejuif cedex
Italy	Research Site	Bologna
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Roma
Poland	Research Site	Warszawa
United States	Research Site	Bronx	New York
United States	Research Site	Dearborn	Michigan
United States	Research Site	Detroit	Michigan
United States	Research Site	Durham	North Carolina
United States	Research Site	Encinitas	California
United States	Research Site	Goldsboro	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Salisbury	Maryland
United States	Research Site	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab	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]))	10 days
Secondary	Percentage of Participants With a Response by Visit	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]))	Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
Secondary	Percentage of Participants With a Complete Response by Visit	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])).	Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57
Secondary	Time to Response	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.	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.
Secondary	Time to Complete Response	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.	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.
Secondary	Duration of Response	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.	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.
Secondary	Duration of Complete Response	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.	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.
Secondary	Time to Relapse/Nonresponse of Hypercalcemia of Malignancy	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.	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.
Secondary	Change From Baseline in Corrected Serum Calcium		Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

External Links

•   AmgenTrials clinical trials website