Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Anti-Arrhythmia Agents

Antihypertensive Agents

Vasodilator Agents

All Drugs and Chemicals

Propranolol

Adrenergic Agents

Adrenergic beta-Antagonists

Adrenergic Antagonists

Neurotransmitter Agents

all subjects will receive the experimental drug

Participants will take 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed

propanolol

Zeina Nahleh, MD

This trial is a Phase II study using the "window-of-opportunity" design in which the treatment-free window between breast cancer diagnosis and surgical tumor resection is used to study the biological effects of the beta blocker propranolol .

* Patients will be recruited from the Garbar Breast Care Center and University Medical Center following diagnosis of invasive breast cancer by breast biopsy.
* The sympatholytic nonselective beta blocker propranolol will be administered to all participants in a non-randomized manner at an equal dose of 1.5 mg/kg/day.
* Following surgical resection of the tumor , the primary endpoint of this study is quantified by comparing the proliferative index of the tumor before propranolol administration (quantified using the initial tumor biopsy) and after 3 weeks of propranolol (quantified using the surgically resected tumor).
* Additional molecular analyses and evaluation of safety and toxicity will also be performed to better understand the effects of this treatment on breast cancers and patient adherence to the drug.

Neoadjuvant Propanolol in Breast Cancer

Pilot "Window of Opportunity" Neoadjuvant Study of Propranolol in Breast Cancer

to evaluate effect of beta adrenergic blockades on breast cancer at by Ki67 percentage change- we are looking at at least 10% mean change in the tumor proliferative index following propranolol treatment

Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.(Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4)

Texas Tech University Health Sciences Center, El Paso

Professor

Zero AEs were reported/observed during and at the end of treatment. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4

all subjects will receive the experimental drug

propanolol: Participants will take 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed

Open Label Single Arm, Drug Propanolol

2 subjects enrolled and received the experimental drug

propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Tumor response by Ki 67

slow accrual was noted , mostly due to scheduling of surgery

Zeina Nahleh

Stage I Patient 1

Stage III Patient 2

We tested the efficacy of propranolol on two patients with breast cancer by recording % reduction of Ki67

Two patients with breast cancer are included in this analysis. One patient was a stage I breast cancer and the second patient was a stage III breast cancer.

Evaluate the Effect of the Beta Blocker Propranolol on Reducing the Tumor Proliferative Index Using Ki-67.

2 subjects enrolled and received the experimental drug

propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed

Both patients reported no AEs due to treatment during treatment phase

Two patients with breast cancer are included in this analysis. One patient was a stage I breast cancer and the second patient was a stage III breast cancer, AEs were assessed during and after treatment

Assess the Safety, Toxicity and Adherence to Propranolol.

2 subjects enrolled and received the experimental drug propanolol: Participants took 1.5 mg/kg/day propranolol, twice daily for 3 weeks until surgical resection of the breast tumor is performed

Overall Study

Diseases and Abnormalities at or Before Birth

Hemangioma

Hemangioma, Capillary

Port-Wine Stain

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

Congenital Abnormalities

Skin Abnormalities

Pharmaceutical Solutions

Acebutolol

Sympathomimetics

Adrenergic beta-1 Receptor Antagonists

10 mg/kg/jour in 2 doses during 90 days after gradual increase of doses in the first week

3 mg/kg/jour in 3 doses during 90 days after gradual increase of doses in the first week

Propanolol

Michèle Bigorre, PH

There is no effective treatment for hemangioma regardless of immediate severity. That is in this respect a orphan disease. These hemangiomas, sometimes large, will have a phase of proliferation of several months (very scary for parents) and regression over several years. The natural history is peppered with local complications (ulcers) and aesthetic and psychological sequelae (sometimes major for the child and the family). The effects of acebutolol and propranolol on the proliferative hemangiomas were discovered accidentally by two French teams (Montpellier for acebutolol and Bordeaux for propranolol). Acebutolol and propranolol have been used for many years for the treatment of hypertension and congenital heart disease, including infants, with few side effects. The effects of acebutolol and propranolol were immediately visible with reduced volume and skin whitening of the hemangioma. In a preliminary study, acebutolol was administered to 20 patients in Montpellier with big regression of hemangiomas. The aim of the study was to compare the clinical efficacy of acebutolol (10mg/Kg/jour) and propranolol (3mg/Kg/j) on the proliferative phase of infantile hemangioma in infants.

Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma

It will be evaluated using a VAS (visual analogue scale) on a series of photos at Day 0, Day 30 and Day 90

All adverse events are collected at each visited

University Hospital, Montpellier

Symptoms and General Pathology

Rare Diseases

Recurrence

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Placebo will be taken daily during the study period

Study participants in the treated group will take 80 mgR propranolol once daily .

Placebo

VINCENZO DE GIORGI, MD

The effectiveness of propranolol in infantile hemangiomas, the apparent better response to propranolol in breast cancer and the use of propranolol in a proportion of patients who did not develop melanoma recurrence suggested to use this unselective β---blocker to test the study hypothesis. The investigators propose a randomized double---blind placebo---controlled clinical trial (RTC) to evaluate whether the treatment with propranolol 80 mgR/die reduce the risk of CMM recurrence and mortality. Patients with resected stage II/IIIA CMM will be recruited in various Centers in Italy. Participants will be randomly assigned to propranolol treatment or placebo (1:1 ratio), treated for at least 1 year and followed for 2 years. Recruitment will proceed simultaneously at the different Centers, and will be completed in 2 years. The primary outcome of the entire trial will be, however, estimated by assessing a reduction in overall mortality at five years. The investigators will also evaluate general CMM recurrence and CMM specific mortality.

Cutaneous malignant melanoma (CMM) represents a major public health problem.Although melanoma accounts for only 4% of all dermatologic cancers, it is responsible for 80% of deaths from skin cancer; only 14% of patients with metastatic melanoma survive for five years . The probability of survival for melanoma stage II/IIIA at 15 years is around 50%.

Treatment with dacarbazine, fotemustine, temozolomide, interferon---α and interleukin---2 has been proposed in metastatic melanoma, but these drugs exert poor efficacy. More recently, ipilimumab, which blocks cytotoxic T---lymphocyte-associated antigen 4 to potentiate an antitumor T---cell response has been approved for the treatment of HLA---A\*0201-positive patients with unresectable stage III or IV melanoma . This treatment has been found to delay mortality by about 4 months, although, in clinical trials a fraction of patients lived much longer . However, the drug caused severe or fatal side effects in almost 13% of patients, prompting the FDA to qualify its approval with a mitigation strategy. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune---related adverse events. These findings do not suggest the use of ipilimumab in non metastatic patients. After surgical resection no specific pharmacotherapy is recommended for patients with stage II/IIIA CMM until metastases are found.

β---adrenoceptor antagonists (β---blockers) belong to one of the most widely used classes of drugs in clinical practice. Their use is mainly directed to the chronic management of hypertension , although they are also prescribed for ischemic heart disease, heart failure, anxiety, tremor, migraine and glaucoma , Initial pharmacoepidemiological evidence shows that β---blockers may reduce cancer risk. Indeed, β--- blockers have been reported to exert a certain degree of protection against prostate cancer . More recently, β---blocker treatment for concomitant diseases has been found to significantly reduce distant metastases, cancer recurrence, and cancer---specific mortality in breast cancer patients .

Infantile hemangiomas are the most common benign tumor of infancy. Over the last few years, propranolol has become a popular and successful treatment for infantile hemangiomas. The ability of ß---adrenoceptors to increase the vascular endothelial growth factor (VEGF) and the subsequent angionenetic pathway has contributed to the identification of this mechanism as a primary target of ß---blockers to limit cancer progression and to treat hemangiomas. The recent observation that propranolol treated successfully a case of infantile lymphangiomatosis and simulatneously reduced VEGF levels further strengthens this hypothesis. Preclinical studies have proposed that activation of β--- adrenoceptors play a detrimental role in melanoma, as in vitro studies showed that melanoma tissues expressed both β1--- and β2---adrenoceptors and that isoproterenol is a potent inducer of VEGF, IL---8 and IL---6 gene expression in human melanoma cells supporting the role of β--- adrenoceptors in this pathway. Thus, the role of ß---adrenoceptors to promote angiogenesis, supported by both basic and clinical evidence, represents the most robust working hypothesis explaining the beneficial effect of ß-blockers indifferent models of cancers,including melanoma.

In a prospective cohort of 121 consecutive patients with thick melanoma (Breslow \>1), the investigators recently found that the use of β---blockers for concomitant diseases for 1 year or more is associated with a reduced risk of CMM recurrence. After a median follow---up time of 2.5 years, tumor progression was observed in 3.3% of the treated (n=30) subgroup and in 34.1% of the untreated (n=91) subgroup . Cox model on progression indicated a 36% (95%CI: 11%---54%; P=.002) risk reduction for each year of β---blocker use. No death was observed in the treated group, whereas in the untreated group 24 patients died. This study suggested for the first time that exposure to β---blockers is associated with a reduced risk of progression of thick CMM. In a larger group of 741 patients with thick and thin CMM the invetigators have recently confirmed the association between β---blocker prescription (79 patients) and the reduction in the risk of CMM recurrence and death.

The investigators hypothesize that treatment with propranolol reduces the risk of recurrence of CMM and decrease overall mortality.

Study Design The investigators propose a randomized double---blind placebo---controlled clinical trial (RTC) to evaluate whether the treatment with propranolol 80 mgR/die reduce the risk of CMM recurrence and mortality. Patients with resected stage II/IIIA CMM will be recruited in various Centers in Italy. Participants will be randomly assigned to propranolol treatment or placebo (1:1 ratio), treated for at least 1 year and followed for 2 years. Recruitment will proceed simultaneously at the different Centers, and will be completed in 2 years. Complete physical examination, measure of study compliance will be performed at baseline, as well as at the interim visits, every 4 months. The primary outcome of the entire trial will be, however, estimated by assessing a reduction in overall mortality at five years. The invetigators will also evaluate general CMM recurrence and CMM specific mortality.

Study population/Study Sites The proposed RCT will be conducted across Dermatology and Plastic Surgery centers primarily in Tuscany and also in other sites in Italy and if necessary in additional European countries. The end of follow-up is determined by recurrence, death, or last day of the follow-up.

Recruitment, Randomization and Treatment Assignment Potential study participants will be recruited among patients treated at Dermatology and Plastic Surgery centers in Tuscany/Italy. All screened subjects at each center will be assigned an ID number irrespective of whether or not they are randomized to receive study treatment. Randomization will be performed using a web---based procedure. Randomization patient numbers for each participant will be generated by computer for each of the two treatment assignments.

Unblinding will be provided once recruitment, data collection, laboratory analyses and whole follow up are completed. Protection of confidentiality will be achieved by limited access to the databases. At baseline the invetigators will also measure anthropometric variables such as weight, height. Arterial blood pressure, pulse rate and ECG will be recorded. Subjects enrolled will be asked about: hormone therapies, statin use; medical conditions such as xeroderma pigmentosum, basal cell nevus syndrome, lupus erythematosus, organ transplantation and immunosuppressive therapy; history of psoriasis; history of depression; all concomitant medications.

The participants will be asked to return to the recruitment clinic for 13 follow---up visits at months 4, 8, 12, 16, 20, 24, 28, 32, 36, 42, 48, 54 and 60. At alternate visits they will receive the next 8 months supply of medication for the study participants. The physician will perform a complete physical examination, including measurement of body weight, blood pressure and pulse rate, to assess the general health of the study participant. We will collect up---dated information about health status and signs of recurrence of melanoma.

Dosage and Administration Study participants will be randomized to 80 mgR propranolol once daily or placebo.

Concomitant medications Patients will be discouraged from taking unspecified medications. However all medications, vitamin and mineral supplements and herbs taken by the participant should be documented on the Case Report Form (CRF) and will include: start and stop date, dose and route of administration, and indication for use.

Methods to monitor adherence The following methods of adherence monitoring will be used: blisters evaluation and subject self--- reporting, in keeping with the current practice of investigators to rely heavily on such tools.

Withdrawal criteria Study Participants will be able to withdraw from the study at any time. Reason for subject discontinuation may include: recurrence, adverse event that compromises the patient's ability to participate in the study, such as serious acute emergencies (i.e., heart attack, stroke or acute abdomen surgery). Subjects who discontinue treatment will be encouraged to participate in the follow---up examinations to maintain an intention---to---treat analysis.

After 3 years of treatment patients will terminate the intervention period and will be followed on an annual basis for 2 years unless the early termination of the study. After 546 patients have been randomized, the accrual will be closed. When the last randomized subject has concluded the 3 years of treatment and 2 years of follow---up, the study will be considered closed. The Data Safety and Monitoring Board (DSMB), the Ethics Committee and regulatory authorities can make the decision to terminate the study earlier. This decision could be based on factors such as unacceptable adverse events, poor accrual or compliance on interim analyses.

Staffing and Scheduling Coordinating Centre for Field Activities: the study will have a study coordination center at the Department of Preclinical and Clinical Pharmacology of the University of Florence, which will coordinate all the different aspects of the study field conduction. Prof. Alessandro Mugelli expert in cardiopharmacology, Prof. Niccolò Marchionni, expert in clinical cardiology and Dr. Sara Gandini, expert in data management and biostatistics will assist Dr. Vincenzo De Giorgi and Prof. Pierangelo Geppetti in the coordination of the study. The clinical investigators led by the PI, Dr. Vincenzo De Giorgi, will be responsible for study recruitment, clinical examination of patients and assessing patient safety. Study set-up will take approximately 6 months and will occur at the beginning of the funding period. After 6 months of study set---up period and 9 years of active data collection period (i.e., time between the first person entering the trial up to the last person completing the final 24 month follow-up visit), the last 6 months will be for study close---out activities. These activities will include final data entry and cleaning, final data analysis, and report writing. The entire study from beginning of study set-up to end of study close-out will take 7 years to be completed (two years of accrual, 3 years of treatment, 2 years of follow-up).

Sample size calculations Results of the previous prospective study on of 741 melanoma patients showed that, after a median follow---up time of 4 years, Cox-regression model on overall mortality indicated a 38% (95%CI: 10%---57%;P=.02) risk reduction for each year of β--blocker use. Cautiously, we considered an hazard ratio of about 0.6 for the randomized placebo-controlled phase-II trial. A total sample size of 546 (split equally between the two groups) will give us 90% of power for estimating a improvement in OS at five years achieves 90% power to detect an improvement given a survival at five years of 0.70 and an increase to 0.82 in the treatment groups)at a significance level (alpha) of 0.05 using a two---sided log rank test. These results assume that 3 sequential tests are made using the O'Brien-Fleming spending function to determine the test boundaries and that the hazards are proportional.

MELABLOCK: A Clinical Trial on the Efficacy and Safety of Propranolol 80 mg in Melanoma Patients

Melablock: A Multicentre Randomized, Double---blinded and Placebo---controlled Clinical Trial on the Efficacy and Safety of Once Daily Propranolol 80 mg Retard for the Prevention of Cutaneous Malignant Melanoma Recurrence

To assess the effect of treatment with propranolol 80 mg retard (R) on overall survival for cutaneous malignant melanoma (CMM) patients in stage II/IIIA (T2, N0 or N1, M0) at five years of follow---up,after at least one year of treatment. Chi-square and Fisher's exact tests will be used to analyze the associations between the categorical variables. Logistic regression adjusting for confounding factors will be also performed. Wilcoxon tests will be used to compare continuous variables. Overall survival and Disease Free Survival curves will be estimated by the Kaplan-Meier method. Log-rank test will be used to compare survival time between groups and Cox proportional hazards models to evaluate the effect of β-blockers treatment and duration of treatment on melanoma recurrence and mortality, considering stratification factors.

To evaluate the effect of treatment on disease free survival (DFS) at five years for CMM patients in stage II/IIIA. Chi-square and Fisher's exact tests will be used to analyze the associations between the categorical variables. Logistic regression adjusting for confounding factors will be also performed. Wilcoxon tests will be used to compare continuous variables. Overall survival and Disease Free Survival curves will be estimated by the Kaplan-Meier method. Log-rank test will be used to compare survival time between groups and Cox proportional hazards models to evaluate the effect of β-blockers treatment and duration of treatment on melanoma recurrence and mortality, considering stratification factors.

To evaluate the effect of treatment on specific mortality for CMM patients in stage II/IIIA. Chi-square and Fisher's exact tests will be used to analyze the associations between the categorical variables. Logistic regression adjusting for confounding factors will be also performed. Wilcoxon tests will be used to compare continuous variables. Overall survival and Disease Free Survival curves will be estimated by the Kaplan-Meier method. Log-rank test will be used to compare survival time between groups and Cox proportional hazards models to evaluate the effect of β-blockers treatment and duration of treatment on melanoma recurrence and mortality, considering stratification factors.

To evaluate the long---term safety of treatment on CMM patients in stage II/IIIA.This study will use the NCI Common Terminology Criteria for Adverse events version 3.0, for toxicity and adverse event reporting. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be found at http://ctep.cancer.gov. AEs will be assessed according to the CTCAE grade associated with the AE term. AEs that do not have a corresponding CTCAE term will be assessed according to their impact on the participant's ability to perform daily activities

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Propanolol in Breast Cancer	NCT02596867	Breast Cancer	propanolol	18 Years - 65 Years	Texas Tech University Health Sciences Center, El Paso
Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma	NCT01743885	Hemangioma	Acebutolol Propanolol	- 6 Months	University Hospital, Montpellier
MELABLOCK: A Clinical Trial on the Efficacy and Safety of Propranolol 80 mg in Melanoma Patients	NCT02962947	Melanoma	Propranolol Placebo	18 Years - 75 Years	Azienda Sanitaria di Firenze
Neoadjuvant Propanolol in Breast Cancer	NCT02596867	Breast Cancer	propanolol	18 Years - 65 Years	Texas Tech University Health Sciences Center, El Paso

Spots Global Cancer Trial Database for propanolol

Every month we try and update this database with for propanolol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for propanolol

Every month we try and update this database with for propanolol cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for propanolol cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.