Study Evaluating the Biologic Activity of Guanabenz in Bone Metastasis

February 8, 2018 updated by: Kathy Miller

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46290
        • Spring Mill Medical Center
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Health Hospital
      • Indianapolis, Indiana, United States, 46202
        • Sidney & Lois Eskenazi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. ≥ 18 years old at the time of informed consent
  2. Ability to provide written informed consent and HIPAA authorization
  3. Solid organ malignancy with documented bone metastasis by imaging
  4. Adequate liver function (serum total bilirubin <= 3 and AST/ALT <= 3 times the upper normal limit)
  5. Adequate renal function (serum creatinine <= 2mg/dL)
  6. Ability to swallow oral tablets

  7. Females of childbearing potential must have a negative pregnancy test <= 28 days prior to registration. All females of childbearing potential who are sexually active, must agree to use a highly reliable method of contraception to prevent pregnancy. These include abstinence, partner with previous vasectomy, placement of an intrauterine device (IUD), condom with spermicidal foam/gel/film/cream/suppository, diaphragm or cervical vault cap, or hormonal birth control (pills or injections).

    NOTE: Females are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses).

  8. Patients are permitted to participate in other clinical trials while participating in this trial.
  9. Patients will receive standard of care systemic treatment for underlying solid malignancy as deemed necessary by treating physician.

Exclusion Criteria:

  1. No prior history of bisphosphonate ordenosumab use in the past 12 months

  2. No history of SRE within past 3 months

    1. Excruciating bone pain requiring RT
    2. Cord compression
    3. Hypercalcemia [serum calcium >10.5]
    4. Pathologic fracture
  3. No history of Paget's disease
  4. No history of epilepsy/seizures
  5. No history of hypotension (defined as resting systolic blood pressure of < 110 mm Hg or diastolic blood pressure of < 70 mm Hg) or orthostasis (defined as drop in systolic blood pressure of >20 mm Hg or increase in HR of > 20 from supine to standing position).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Guanabenz
Drug: Guanabenz acetate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bone Turnover Markers-bone Formation and Bone Resorption
Time Frame: Day 0, Week 8, Week 12
Number of patients who had blood specimens taken to collect and evaluate markers of bone formation and bone resorption. Note - due to poor accrual and early closure, bone marker data was not collected.
Day 0, Week 8, Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Treatment Related Adverse Events
Time Frame: Up to 1 year
Number of unique patients who had a treatment related (possible, probable or definite) adverse events.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Kathy Miller

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kathy Miller, MD, Indiana University (IU) School of Medicine, Department of Medicine; IU Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 7, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 8, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 8, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 13, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IUCRO-0506

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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