Ignite Creation Date:
2025-12-24 @ 7:17 PM
Ignite Modification Date:
2026-01-03 @ 11:11 PM
Study NCT ID:
NCT02443103
Status:
TERMINATED
Last Update Posted:
2018-02-13
First Post:
2015-05-11
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study Evaluating the Biologic Activity of Guanabenz in Bone Metastasis
Sponsor:
Kathy Miller
Organization:
Study Overview
Official Title:
Exploratory Pilot Study Evaluating the Biologic Activity of Guanabenz in Bone Metastasis
Status:
TERMINATED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will explore the biologic activity of guanabenz in reducing bone turn over in solid tumor patients with bone metastasis. If successful, this repurposing of an already, generic drug could benefit patients faster than manufacturing a novel expensive compound.
Detailed Description:
OBJECTIVES Primary Objective: Evaluate the biologic effect of guanabenz on markers of bone formation and bone resorption in patients with solid tumors and bone metastasis.
Secondary Objectives: (1) Compare guanabenz exposure in patients based on limited PK sampling to activity observed in previous pre-clinical studies; (2) Assess the safety/tolerability of guanabenz; and (3) Evaluate the biologic effect of guanabenz on bone metabolism markers.
Tertiary Objective: Compare change in bone turn over markers (formation, resorption and metabolism) achieved with guanabenz to change in bone turn over markers with standard of care (bisphosphonate/denosumab).
STUDY DESIGN This is an exploratory pilot study evaluating the biologic effect of guanabenz bone formation and bone resorption markers in patients with solid tumors and bone metastasis.
PROCEDURES All registered patients will receive oral guanabenz the first two months prior to the start of any standard of care skeletal protective therapy. All patients on study will receive standard of care systemic treatment for their underlying solid malignancy as deemed necessary by their treating physician. Guanabenz will be administered concurrently with any primary cancer systemic treatment. However patients will withhold standard of care bone directed therapy for 8 weeks. The study will exclude patients in immediate need of such treatment. Patients experiencing skeletal related events while on study will be withdrawn. Delaying standard of care skeletal therapy for 2 months will not be considered a major deviation as long as such therapy is delayed for a necessary purpose as deemed by the treating physician.
Patients with known hypertension and on antihypertensive medications at study enrollment will be eligible to participate. Antihypertensive medications will not be changed as a result of study enrollment unless deemed necessary by the treating physician; only the dose of guanabenz will be adjusted.
TREATMENT Patients will begin taking 8 mg by mouth (PO) at bed time (HS) starting day 1 for one week. The dose will be increased to 8 mg PO twice a day (BID) (8 mg daily morning (QAM) and 8 mg daily evening (QPM) for a total of 16 mg) on day 8 (+/-3 days), then increased to 8 mg PO QAM 16 mg PO QPM (total of 24 mg) on day 15 (+/- 3 days), then increased to 16 mg PO BID (16 mg QAM and 16 mg QPM for a total of 32 mg) on day 22. Patients will continue on their maximum tolerated dose (MTD) until day 56 (+/- 3 days). The dose will be weaned for patients receiving more than 8 mg daily after completing week 8 when the standard of care skeletal protective therapy begins. Guanabenz will be weaned off by week 11, and patients will continue standard of care skeletal protective therapy as deemed necessary by the treating physician.
To ensure patient safety during dose escalation and throughout the study, patients will be provided and taught the use of home blood pressure (BP) monitoring. We will instruct patients to check their BP 2 hours after each guanabenz dose escalation and at least three times weekly. Patients will maintain a diary of BP results during the dose escalation phase. Patients will report any hypotensive measurement to their research nurse defined as at least two readings less than \< 100/60 mm Hg in sitting position taken more than 30 min apart.
At each visit, blood pressure and adverse events will be assessed. Dose escalation will continue with guanabenz if BP \>= 110/70 mm Hg and/or until unacceptable toxicity.
Guanabenz should be taken as instructed on an empty stomach. If the patient misses a dose of guanabenz, he/she can take the missing dose no later than 3 hours after instructed time and then continue as scheduled.
On day 57 (+/- 3 days), all study patients start the guanabenz wean. All patients will receive ongoing standard of care skeletal protective therapy (denosumab/zometa) as determined by the treating physician at the beginning of the weaning phase.
Secondary Objectives: (1) Compare guanabenz exposure in patients based on limited PK sampling to activity observed in previous pre-clinical studies; (2) Assess the safety/tolerability of guanabenz; and (3) Evaluate the biologic effect of guanabenz on bone metabolism markers.
Tertiary Objective: Compare change in bone turn over markers (formation, resorption and metabolism) achieved with guanabenz to change in bone turn over markers with standard of care (bisphosphonate/denosumab).
STUDY DESIGN This is an exploratory pilot study evaluating the biologic effect of guanabenz bone formation and bone resorption markers in patients with solid tumors and bone metastasis.
PROCEDURES All registered patients will receive oral guanabenz the first two months prior to the start of any standard of care skeletal protective therapy. All patients on study will receive standard of care systemic treatment for their underlying solid malignancy as deemed necessary by their treating physician. Guanabenz will be administered concurrently with any primary cancer systemic treatment. However patients will withhold standard of care bone directed therapy for 8 weeks. The study will exclude patients in immediate need of such treatment. Patients experiencing skeletal related events while on study will be withdrawn. Delaying standard of care skeletal therapy for 2 months will not be considered a major deviation as long as such therapy is delayed for a necessary purpose as deemed by the treating physician.
Patients with known hypertension and on antihypertensive medications at study enrollment will be eligible to participate. Antihypertensive medications will not be changed as a result of study enrollment unless deemed necessary by the treating physician; only the dose of guanabenz will be adjusted.
TREATMENT Patients will begin taking 8 mg by mouth (PO) at bed time (HS) starting day 1 for one week. The dose will be increased to 8 mg PO twice a day (BID) (8 mg daily morning (QAM) and 8 mg daily evening (QPM) for a total of 16 mg) on day 8 (+/-3 days), then increased to 8 mg PO QAM 16 mg PO QPM (total of 24 mg) on day 15 (+/- 3 days), then increased to 16 mg PO BID (16 mg QAM and 16 mg QPM for a total of 32 mg) on day 22. Patients will continue on their maximum tolerated dose (MTD) until day 56 (+/- 3 days). The dose will be weaned for patients receiving more than 8 mg daily after completing week 8 when the standard of care skeletal protective therapy begins. Guanabenz will be weaned off by week 11, and patients will continue standard of care skeletal protective therapy as deemed necessary by the treating physician.
To ensure patient safety during dose escalation and throughout the study, patients will be provided and taught the use of home blood pressure (BP) monitoring. We will instruct patients to check their BP 2 hours after each guanabenz dose escalation and at least three times weekly. Patients will maintain a diary of BP results during the dose escalation phase. Patients will report any hypotensive measurement to their research nurse defined as at least two readings less than \< 100/60 mm Hg in sitting position taken more than 30 min apart.
At each visit, blood pressure and adverse events will be assessed. Dose escalation will continue with guanabenz if BP \>= 110/70 mm Hg and/or until unacceptable toxicity.
Guanabenz should be taken as instructed on an empty stomach. If the patient misses a dose of guanabenz, he/she can take the missing dose no later than 3 hours after instructed time and then continue as scheduled.
On day 57 (+/- 3 days), all study patients start the guanabenz wean. All patients will receive ongoing standard of care skeletal protective therapy (denosumab/zometa) as determined by the treating physician at the beginning of the weaning phase.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: