Propranolol Hydrochloride in Treating Patients With Locally Recurrent or Metastatic Solid Tumors That Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Ohio State University Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
William Carson, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02013492
First received: December 11, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This pilot trial studies propranolol hydrochloride in treating patients with locally recurrent or metastatic solid tumors that cannot be removed by surgery. Propranolol hydrochloride may slow the growth of tumor cells by blocking the use of hormones by the tumor cells.


Condition Intervention
Male Breast Cancer
Recurrent Melanoma
Stage IV Breast Cancer
Stage IV Melanoma
Stage IV Ovarian Epithelial Cancer
Stage IV Ovarian Germ Cell Tumor
Unspecified Adult Solid Tumor, Protocol Specific
Drug: propranolol hydrochloride
Other: Correlative Studies

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Beta-Blockers in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events (CTCAE) V. 4.0 [ Time Frame: Up to 4 months ] [ Designated as safety issue: Yes ]
    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.

  • Change in vascular endothelial growth factor (VEGF) [ Time Frame: Baseline to 4 months ] [ Designated as safety issue: No ]
  • Effect of beta-adrenergic blockade on the tumor microenvironment [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    Measured via a series of correlative laboratory studies using cancer tumor tissue and peripheral blood mononuclear cells.

  • Effect of beta-adrenergic blockade on the host immune system [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    Measured via a series of correlative laboratory studies using cancer tumor tissue and peripheral blood mononuclear cells.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: January 2014
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: propranolol hydrochloride
Given PO
Other Name: Inderal
Other: Correlative Studies

Correlative studies will be conducted using the following materials:

  • Plasma derived from peripheral blood.
  • Peripheral blood mononuclear cells (PBMC) derived from patient blood
  • Tumor tissue obtained at the time of core needle biopsy at the 2 month time point.
  • Paraffin-embedded tumor tissue obtained pre-therapy to make the diagnosis of metastatic disease.

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the feasibility and tolerability of beta-adrenergic blockade in patients with metastatic 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • 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
  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02013492

Contacts
Contact: The Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu
Contact: William Carson, MD 614-293-6306 William.Carson@osumc.edu

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: William E. Carson, MD    614-293-6306    william.carson@osumc.edu   
Principal Investigator: William E. Carson, MD         
Sponsors and Collaborators
William Carson
Investigators
Principal Investigator: William Carson, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: William Carson, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02013492     History of Changes
Other Study ID Numbers: OSU 13023, NCI-2013-01958
Study First Received: December 11, 2013
Last Updated: July 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Beta-Blocker
metastatic melanoma

Additional relevant MeSH terms:
Breast Neoplasms
Melanoma
Neoplasms, Germ Cell and Embryonal
Breast Neoplasms, Male
Germinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Adrenergic beta-Antagonists
Propranolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014