Effect of CTAP101 Capsules on Ca/iPTH in Advanced Breast/Prostate Cancer Patients Treated With Denosumab/Zoledronic Acid
Primary Purpose
Breast Cancer, Prostate Cancer, Bone Neoplasms
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CTAP101 Capsules
Sponsored by
About this trial
This is an interventional supportive care trial for Breast Cancer focused on measuring Bone Neoplasms, Hypocalcemia, Hyperparathyroidism, Secondary
Eligibility Criteria
Inclusion Criteria:
- Be diagnosed with bone metastases subsequent to breast (female subjects only) or prostate carcinoma, and will have received zoledronate or denosumab therapy for at least 3 months at the time of enrollment
- Be at least 18 years of age
- Have a life expectancy >12 months from the anticipated time of initiation of treatment
- Serum calcium <9.8 mg/dL
- Plasma iPTH ≥70 pg/mL if taking <1200 IU vitamin D
- Estimated glomerular filtration rate (GFR) >15 mL/min/1.73m2
- If taking more than 1000 mg/day of elemental calcium, must be willing and able to discontinue or reduce their calcium use and/or use non-calcium based therapies for the duration of the study
- Subjects receiving ≤2000 IU/day vitamin D (ergocalciferol or cholecalciferol) therapy must remain on a stable dose during the study. If taking more than 2000 IU/day of vitamin D (ergocalciferol or cholecalciferol), must be willing and able to reduce use to ≤2000 IU/day and remain on a stable dose for the duration of the study
- Is willing and able to comply with study instructions and commit to all clinic visits for the duration of the study
- Female subject of childbearing potential is neither pregnant nor lactating and must have a negative pregnancy test at the screen visit and a negative pregnancy test before dosing. All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device (IUD), sexual abstinence, vasectomy or vasectomized partner) for the duration of the study
- Has the ability to read and understand subject Informed Consent Form (ICF).
Exclusion Criteria:
- Spot urine Ca:Cr ratio >0.25 (>250 mg/g creatinine)
- Known previous or concomitant serious illness (other than advanced cancer with metastatic bone disease) or medical condition, such as, HIV, significant gastrointestinal disease, or cardiovascular event that in the opinion of the investigator may worsen and/or interfere with participation in the study
- History of neurological/psychiatric disorder, including psychotic disorder or dementia, or any other reason, which in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely
- Known or suspected hypersensitivity to any of the constituents of the investigational product
Sites / Locations
- Coast Hematology-Oncology Associates
- Mount Sinai Medical Center, Comprehensive Cancer Center
- Research by Design LLC
- Roswell Park Cancer Institute
- University of Cincinnati Cancer Institute
- Inova Dwight and Martha Schar Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CTAP101 Capsules
Arm Description
CTAP101 Capsules daily
Outcomes
Primary Outcome Measures
Effect of repeated, escalating doses of CTAP101 on serum calcium and plasma iPTH levels
Effect of repeated, escalating daily doses of CTAP101 on serum calcifediol
Safety and tolerability of CTAP101
Measured by the number of participants with treatment related adverse events and abnormal physical examinations, vital signs, clinical laboratory tests (hematology, coagulation, and clinical chemistry, urine calcium, albumin and creatinine), and 12-lead ECG.
Secondary Outcome Measures
Effect of repeated, escalating daily doses of CTAP101 on vitamin d metabolites
Effect of repeated, escalating doses of CTAP101 on serum phosphorus and spot urine calcium:creatinine ratio
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02274623
Brief Title
Effect of CTAP101 Capsules on Ca/iPTH in Advanced Breast/Prostate Cancer Patients Treated With Denosumab/Zoledronic Acid
Official Title
Effect of CTAP101 Capsules on Serum Calcium, Plasma Intact Parathyroid Hormone and Vitamin D Metabolites in Patients With Advanced Breast or Prostate Carcinomas With Metastases to Bone and Receiving Ongoing Therapy With Denosumab or Zoledronic Acid
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
February 27, 2017 (Actual)
Study Completion Date
March 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OPKO Health, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label exploratory study of CTAP101 Capsules in patients with bone metastases arising from either breast or prostate cancer, who are taking anti-resorptive therapy.
Detailed Description
This is a multi-center, open-label, repeat-dose study to evaluate the safety, efficacy, and tolerability of CTAP101 Capsules in subjects with bone metastases who are receiving ongoing therapy with denosumab or zoledronic acid. Following screening, approximately 12 eligible subjects with breast cancer and approximately 12 eligible subjects with prostate cancer, all of whom have metastases to bone and are undergoing treatment with anti-resorptive therapies, will receive CTAP101 Capsules at an initial daily oral dose of 30 μg (1 capsule) for 4 weeks. The daily dose may be increased in 30 μg (1 capsule) increments at 4-week intervals to a maximum of 300 μg or until serum calcium reaches >10.3 mg/dL for two consecutive visits (dose escalation phase) at which time the subject will suspend dosing until serum calcium is ≤10.0 mg/dL and will directly enter a 12-week maintenance phase, resuming treatment at a reduced daily dose, followed by a 2-week follow-up period. Subjects reaching the maximum dose without serum calcium reaching >10.3 mg/dL, will directly enter the 12-week maintenance phase, followed by a 2-week follow-up period. Serum markers for monitoring bone metabolism (including plasma iPTH, PTHrP, and serum free calcifediol), immune function and tumor burden will be measured during the treatment period. The FACT-BP Quality of Life Measurement in Patients with Bone Pain questionnaire will be used to explore the effect of the treatment, if any, on musculoskeletal pain. The genotype of vitamin D binding protein (DBP) will also be determined. Safety will be monitored through adverse events, serum and urine chemistries, hematology, and ECGs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Prostate Cancer, Bone Neoplasms, Hypocalcemia, Hyperparathyroidism, Secondary
Keywords
Bone Neoplasms, Hypocalcemia, Hyperparathyroidism, Secondary
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CTAP101 Capsules
Arm Type
Experimental
Arm Description
CTAP101 Capsules daily
Intervention Type
Drug
Intervention Name(s)
CTAP101 Capsules
Other Intervention Name(s)
calcifediol
Intervention Description
escalating doses
Primary Outcome Measure Information:
Title
Effect of repeated, escalating doses of CTAP101 on serum calcium and plasma iPTH levels
Time Frame
up to 52 weeks
Title
Effect of repeated, escalating daily doses of CTAP101 on serum calcifediol
Time Frame
up to 52 weeks
Title
Safety and tolerability of CTAP101
Description
Measured by the number of participants with treatment related adverse events and abnormal physical examinations, vital signs, clinical laboratory tests (hematology, coagulation, and clinical chemistry, urine calcium, albumin and creatinine), and 12-lead ECG.
Time Frame
up to 52 weeks
Secondary Outcome Measure Information:
Title
Effect of repeated, escalating daily doses of CTAP101 on vitamin d metabolites
Time Frame
up to 52 weeks
Title
Effect of repeated, escalating doses of CTAP101 on serum phosphorus and spot urine calcium:creatinine ratio
Time Frame
up to 52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be diagnosed with bone metastases subsequent to breast (female subjects only) or prostate carcinoma, and will have received zoledronate or denosumab therapy for at least 3 months at the time of enrollment
Be at least 18 years of age
Have a life expectancy >12 months from the anticipated time of initiation of treatment
Serum calcium <9.8 mg/dL
Plasma iPTH ≥70 pg/mL if taking <1200 IU vitamin D
Estimated glomerular filtration rate (GFR) >15 mL/min/1.73m2
If taking more than 1000 mg/day of elemental calcium, must be willing and able to discontinue or reduce their calcium use and/or use non-calcium based therapies for the duration of the study
Subjects receiving ≤2000 IU/day vitamin D (ergocalciferol or cholecalciferol) therapy must remain on a stable dose during the study. If taking more than 2000 IU/day of vitamin D (ergocalciferol or cholecalciferol), must be willing and able to reduce use to ≤2000 IU/day and remain on a stable dose for the duration of the study
Is willing and able to comply with study instructions and commit to all clinic visits for the duration of the study
Female subject of childbearing potential is neither pregnant nor lactating and must have a negative pregnancy test at the screen visit and a negative pregnancy test before dosing. All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device (IUD), sexual abstinence, vasectomy or vasectomized partner) for the duration of the study
Has the ability to read and understand subject Informed Consent Form (ICF).
Exclusion Criteria:
Spot urine Ca:Cr ratio >0.25 (>250 mg/g creatinine)
Known previous or concomitant serious illness (other than advanced cancer with metastatic bone disease) or medical condition, such as, HIV, significant gastrointestinal disease, or cardiovascular event that in the opinion of the investigator may worsen and/or interfere with participation in the study
History of neurological/psychiatric disorder, including psychotic disorder or dementia, or any other reason, which in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely
Known or suspected hypersensitivity to any of the constituents of the investigational product
Facility Information:
Facility Name
Coast Hematology-Oncology Associates
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Mount Sinai Medical Center, Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Research by Design LLC
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Inova Dwight and Martha Schar Cancer Center
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Effect of CTAP101 Capsules on Ca/iPTH in Advanced Breast/Prostate Cancer Patients Treated With Denosumab/Zoledronic Acid
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