- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02013492
Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery
A Pilot Study of Beta-Blockers in Patients With Advanced Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the feasibility and tolerability of beta-adrenergic blockade in patients with metastatic or locally advanced cancer.
II. To determine the effects of beta-adrenergic blockade on the tumor microenvironment and host immune system via a series of correlative laboratory studies using cancer tumor tissue and peripheral blood mononuclear cells from the study patients.
SECONDARY OBJECTIVES:
I. Evaluate the effects of beta-adrenergic blockade on progression-free survival and overall survival.
OUTLINE:
Patients receive propranolol hydrochloride orally (PO) twice daily (BID) for 4 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 1 year.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have histologically-proven locally-recurrent or metastatic solid tumor; the first 10 patients may have cancer of any histology; preference will be given to patients with metastatic ovarian cancer, breast cancer, and malignant melanoma, as these malignancies have been shown to be sensitive to manipulation of the beta-adrenergic receptor; the final twenty-five patients to be accrued must have locally-recurrent or metastatic malignant melanoma that is not surgically resectable. An additional cohort of 10 patients with BCLC stages A to C locally advanced or metastatic hepatocellular carcinoma (HCC) that is not surgically resectable will also be enrolled (See appendix for BCLC staging system). Patients with liver transplantation will not be eligible.
The diagnosis of hepatocellular carcinoma may be made by one of the following methods:
- Pathologically (histologically or cytologically) proven diagnosis of HCC.
- At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multiphasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
- For patients whose CURRENT disease is vascular only: Enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed according to criteria in (a) or (b).
- Patients may have had any number of prior systemic therapies; patients need not have exhausted standard therapy for their disease, but must be stable and must not have actively progressing
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Karnofsky >= 60%
- Life expectancy of greater than 6 months
- Patients (except for the HCC cohort) must have normal organ and marrow function as defined below:
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR
- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Parameters for the HCC cohort:
- leukocytes > or = 3000/mcl
- absolute neutrophil count > or =1000/mcl
- platelets > or = 70,000
- total bilirubin < or = 2mg/dL
- AST/ALT <6 times ULN
- creatinine within normal institutional limits OR
- creatinine clearance > or = 60mL/min/1.73m2 for patients with creatinine levels above institutional normal level
- INR < or = 1.7
- The effects of propranolol on the developing human fetus may be detrimental. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients with brain metastases may participate in this clinical study provided that symptoms have been controlled with standard therapies and/or appropriate medications; the principal investigator (P.I.) will carefully evaluate the suitability of patient participation when brain metastases are present
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to propranolol
- Uncontrolled hypertension
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with significant lung disease, an ejection fraction less than 40%, or a resting heart rate less than 60/min will not be enrolled
- Pregnant women are excluded from this study because propranolol is an agent with the potential for teratogenic or abortifacient effects
- Patients who are currently receiving a beta-blocker for another medical condition will be excluded from this study; patients with extremes of blood pressure (e.g., systolic blood pressure [SBP] > 150 or < 100) may be excluded from participation if the treating physician feels that this medical condition has not been adequately addressed by the patient's primary care physician
- Patients with worsening depression that has not been addressed clinically will be excluded from this study
Study Plan
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 |
Intervention / Treatment |
---|---|
Experimental: Treatment (propranolol hydrochloride)
Patients receive propranolol hydrochloride PO BID for 4 months in the absence of disease progression or unacceptable toxicity.
Propranolol will be administered on an out-patient basis.
Blood for correlative studies (30 ml - green top tube) will be drawn at baseline and at each clinic visit.
Tumor tissue for analysis will be obtained via core needle biopsy (or other appropriate modality) pre-study and at approximately the two month time point.
|
Given PO
Other Names:
Correlative studies will be conducted using the following materials:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events (CTCAE) V. 4.0
Time Frame: Up to 4 months
|
A dose-limiting toxicity (DLT) will be considered as any grade 3 or higher hematologic or non- hematologic toxicity that is probably or definitely related to treatment.
|
Up to 4 months
|
Change in vascular endothelial growth factor (VEGF)
Time Frame: Baseline to 4 months
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Baseline to 4 months
|
|
Effect of beta-adrenergic blockade on the tumor microenvironment
Time Frame: Up to 4 months
|
Measured via a series of correlative laboratory studies using cancer tumor tissue and peripheral blood mononuclear cells.
|
Up to 4 months
|
Effect of beta-adrenergic blockade on the host immune system
Time Frame: Up to 4 months
|
Measured via a series of correlative laboratory studies using cancer tumor tissue and peripheral blood mononuclear cells.
|
Up to 4 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression-free survival
Time Frame: Up to 1 year
|
Up to 1 year
|
Overall survival
Time Frame: Up to 1 year
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Skin Diseases
- Neoplasms by Histologic Type
- Urogenital Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Breast Diseases
- Liver Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Liver Neoplasms
- Neuroendocrine Tumors
- Nevi and Melanomas
- Ovarian Neoplasms
- Neoplasms
- Breast Neoplasms
- Carcinoma, Hepatocellular
- Melanoma
- Carcinoma, Ovarian Epithelial
- Breast Neoplasms, Male
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Propranolol
Other Study ID Numbers
- OSU 13023
- NCI-2013-01958 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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