Metastasis Clinical Trial
Official title:
Exploratory Pilot Study Evaluating the Biologic Activity of Guanabenz in Bone Metastasis
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.
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 Patients experiencing skeletal related events while on study will be withdrawn.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.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT01441115 -
ECI301 and Radiation for Advanced or Metastatic Cancer
|
Phase 1 | |
Terminated |
NCT03257722 -
Pembrolizumab + Idelalisib for Lung Cancer Study
|
Phase 1/Phase 2 | |
Recruiting |
NCT01201096 -
Neo-adjuvant Peptide Receptor Mediated Radiotherapy With 177Lutetium in Front of Curative Intended Liver Transplantation in Patients With Hepatic Metastasis of Neuroendocrine Tumors (NEO-LEBE)
|
N/A | |
Completed |
NCT01199822 -
Study of the Safety and Pharmacokinetics of IMC-3G3 in Japanese Patients With Solid Tumors
|
Phase 1 | |
Completed |
NCT01206530 -
FOLFOX/Bevacizumab/Hydroxychloroquine (HCQ) in Colorectal Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT00377936 -
EndoTAG-1 / Gemcitabine Combination Therapy to Treat Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas
|
Phase 2 | |
Completed |
NCT00313859 -
Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic CRC
|
Phase 2 | |
Recruiting |
NCT05095207 -
Abemaciclib in Combination With Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04392479 -
TWICE-IRI: Optimization of Second-line Therapy With Aflibercept, Irinotecan (Day 1 or Day 1,3), 5-Fluorouracile and Folinic Acid in Patients With Metastatic Colorectal Cancer. A Randomized Phase III Study.
|
Phase 3 | |
Recruiting |
NCT04808466 -
Comparative Study of Lobaplatin and Paclitaxel in Advanced Gastric Cancer Patients With D2 Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy
|
Phase 2 | |
Terminated |
NCT03652493 -
Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway
|
Phase 2 | |
Not yet recruiting |
NCT04845490 -
Comparative Study of Mitomycin and Lobaplatin in Advanced Colorectal Cancer Patients With Radical Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy
|
Phase 2 | |
Recruiting |
NCT05061082 -
Genomic Evolution of Metastasis in Gastric Cancer
|
||
Not yet recruiting |
NCT06055764 -
Role of FDG PET/CT in Patients With Metastasis of Unknown Origin
|
||
Terminated |
NCT02796729 -
CEST- Glucose Enhanced MRI for Metastatic Brain Tumours
|
Phase 2 | |
Withdrawn |
NCT01157039 -
A Trial of Glutamine to Prevent Oxaliplatin Neurotoxicity and a Pharmacokinetic Analysis of Oxaliplatin
|
Phase 2 | |
Terminated |
NCT01000948 -
A Safety Study of ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer
|
Phase 2 | |
Terminated |
NCT01613482 -
TraStuzumAb-Radiotherapy : Impact on the Cerebral Prevention
|
Phase 3 | |
Withdrawn |
NCT00244348 -
Hepatic Artery Infusion With Oxaliplatin
|
Phase 1/Phase 2 | |
Recruiting |
NCT04416165 -
Comparison of FDG and FAPI in Patients With Various Types of Cancer
|
N/A |