Extended-release of Octreotide (LF-PB) for the Treatment of Lymphorrhea

Study Overview
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Brief Summary
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This is a phase II, multicenter, double-blind, double-dummy, parallel-group, placebo-controlled, study to evaluate LF-PB versus placebo in female patients with brest cancer who are undergoing breast surgery with axillary lymphnode dissection. Recruited patients will be randomly assigned to one of the following treatment groups: Placebo, LF-PB 10 mg, LF-PB 20 mg and LF-PB 30 mg. Mode of administration is single intramuscular (IM) injection so the treatments arms are as follows: Placebo: 2 injections of placebo LF-PB 10 mg: 2 injections = placebo + 10 mg LF-PB 20 mg: 2 injections = placebo + 20 mg LF-PB 30 mg: 2 injections = 10 mg + 20 mg The study will randomize a total of 120 patients (30 per arm) in about 10 Italian Sites.

Official Title
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A Randomized, Double-Blind, Double Dummy, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy of LF-PB 10 mg, 20 mg, and 30 mg to Treat Lymphorrhea Post Axillary Dissection in Breast Cancer

Conditions
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Lymphorrhea

Intervention / Treatment
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* Drug: LF-PB and Placebo
* Drug: Placebo
* Drug: LF-PB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female aged 18 to 80 years inclusive Body mass index (BMI) ≥18 kg/m2 Signed informed consent form Diagnosis of BC Undergoing breast surgery with ALND Note: Collagen powder or fibrin sealant are not permitted. Negative serum pregnancy test for women of childbearing potential Note: Female patients of child-bearing potential should be advised to use adequate contraception if necessary during treatment with octreotide. AST and alanine aminotransferase ALT <1.5 x the upper limit of normal Ability to fully understand all study procedures and to comply with study visits scheduled for the duration of the study. Exclusion Criteria: Presence of any of the following conditions: Previous axillary surgery on the same armpit undergoing surgery in this study Previous chemotherapy or radiotherapy within five years from study drug administration Previous neoadjuvant therapy Recurrent BC on the same breast undergoing surgery in this study Diabetes Cholelithiasis Hypothyroidism. If patient is being administered Euritox/ Levothyroxine (or analogues) and levels of T3, T4 and TSH are confirmed to be within the normal ranges at screening, the patient can be enrolled in this study. Hepatitis Pregnant or lactating Human immunodeficiency virus or hepatitis B or C by screening serology History of radiotherapy on the same breast or armpit undergoing surgery in this study. History of anaphylaxis to study drug Ascertained or presumptive hypersensitivity to the active principle and/or the ingredients of the study drug formulation QTc interval extension at screening or baseline > 450 msec (as the mean of 3 consecutive readings 5 minutes apart) Presence of any disease or use of concomitant medication known to increase the QT interval (see Appendix 2 for a list of such compounds) Clinically significant or relevant abnormal medical history, vital sign, physical examination, ECG, or laboratory evaluation finding Current or recurrent disease that could affect the results of the clinical or laboratory assessments required for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LF-PB 10 mg<br>2 IM injections = placebo + 10 mg | Drug: LF-PB and Placebo<br> <br> * Other names: extended-release of octreotide and placebo;|
| Experimental: LF-PB 20 mg<br>2 IM injections = placebo + 20 mg | Drug: LF-PB and Placebo<br> <br> * Other names: extended-release of octreotide and placebo;|
| Experimental: LF-PB 30 mg<br>2 IM injections = 10 mg + 20 mg | Drug: LF-PB<br> <br> * Other names: LF-PB 10 mg and LF-PB 20 mg;|
| Placebo Comparator: Placebo<br>2 IM injections of placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of LF-PB 10 mg, 20 mg, and 30 mg on time to resolution of lymphorrhea; | End of lymphorrhea will be declared when the lymph volume measured by the patient is < 50 ml/day in 2 consecutive days. | 12 weeks post surgery | 
| number of AEs and laboratory, ECG, vital sign abnormalities of LF-PB 10 mg, 20 mg, and 30 mg | Safety and tolerability of LF-PB | 12 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effects of LF-PB 10, 20, and 30 mg on the daily volume of lymph collected from the drain | daily volume of lymph collected from the drain | 12 weeks after surgery | 
| number of complications related to lymphorrhea | effect of LF-PB 10, 20 and 30 mg on complications related to lymphorrhea | 12 weeks after surgery | 
| PK profile (Cmax, Tmax, AUC0-t and possibly AUC0-inf and T1/2) of LF-PB 10, 20 and 30 mg | PK parameters | 12 weeks after surgery |