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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphorrhea
• Intervention / Treatment: Drug: Placebo; Drug: LF-PB and Placebo; Drug: LF-PB

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Corso Spezia, 60 Torino, Italy, 10126
    • Azienda Ospedaliera OIRM Sant'Anna Dipartimento Funzionale di Oncologia - Breast Unit
  • L.go Rosanna Benzi,10 Genova, Italy, 16132
    • IRCCS Azienda Ospedaliero Universitaria San Martino di Genova - IST Genova Dipartimento Chirurgia Ospedaliera - Semeiotica Chirurgica e Chirurgia Senologica
  • Piazza Giulio Cesare 11 Bari, Italy, 70124
    • Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari Chirurgia Generale Universitaria "G.Marinaccio"
  • Pisa, Italy, 56123
    • Azienda Ospedaliero-Universitaria Di Pisa
  • Roma, Italy, 00128
    • Universita' Campus Bio-Medico Di Roma
  • San Giovanni Rotondo, Italy, 71013
    • Ospedale Casa Sollievo della Sofferenza - Istituto di Ricovero e Cura a Carattere Scientifico Opera di San Pio da Pietrelcina
  • Strada Provinciale 142 Km 3.95- Candiolo, Italy, 10060
    • Fondazione del Piemonte per l'Oncologia - IRCC Candiolo D.O. di Ginecologia Oncologica
  • Via Gramsci, 14 Parma, Italy, 43126
    • Azienda Ospedaliero-Universitaria di Parma Dipartimento Clinica Chirurgica e Terapia Chirurgica
  • Via Mariano Semmola Napoli, Italy, 80131
    • IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione Giovanni Pascale Dipartimento di Senologia - Struttura Complessa Oncologia Medica Senologica
  • Via Pozzo 71, Modena, Italy, 41124
    • Azienda Ospedaliero Universitaria Policlinico di Modena Unità Semplice di Senologia
  • Vial Aldo Moro 8, Cona-Ferrara, Italy, 44124
    • Azienda Ospedaliero Universitaria di Ferrara c/o Ospedale di Cona Sezione di Clinica Chirurgica
  • Catania
    • Via V.E. Dabormida, 64, Catania, Italy, 95125
      • Humanitas Centro Catanese di Oncologia Dipartimento di Oncologia -Chirurgia Oncologica Generale
  • Catanzaro
    • Viale Europa-Loc. Germaneto, Catanzaro, Italy, 88100
      • Fondazione per la Ricerca e la Cura dei Tumori "Tommaso Campanella" Unità Operativa Complessa CRR per il Counselling Genetico e le Terapie Innovative in Oncologia Medica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female aged 18 to 80 years inclusive
2. Body mass index (BMI) ≥18 kg/m2
3. Signed informed consent form
4. Diagnosis of BC
5. Undergoing breast surgery with ALND Note: Collagen powder or fibrin sealant are not permitted.
6. 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.
7. AST and alanine aminotransferase ALT <1.5 x the upper limit of normal
8. Ability to fully understand all study procedures and to comply with study visits scheduled for the duration of the study.

Exclusion Criteria:

1. Presence of any of the following conditions:

   1. Previous axillary surgery on the same armpit undergoing surgery in this study
   2. Previous chemotherapy or radiotherapy within five years from study drug administration
   3. Previous neoadjuvant therapy
   4. Recurrent BC on the same breast undergoing surgery in this study
   5. Diabetes
   6. Cholelithiasis
   7. 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.
   8. Hepatitis
   9. Pregnant or lactating
   10. Human immunodeficiency virus or hepatitis B or C by screening serology
2. History of radiotherapy on the same breast or armpit undergoing surgery in this study.
3. History of anaphylaxis to study drug
4. Ascertained or presumptive hypersensitivity to the active principle and/or the ingredients of the study drug formulation
5. QTc interval extension at screening or baseline > 450 msec (as the mean of 3 consecutive readings 5 minutes apart)
6. Presence of any disease or use of concomitant medication known to increase the QT interval (see Appendix 2 for a list of such compounds)
7. Clinically significant or relevant abnormal medical history, vital sign, physical examination, ECG, or laboratory evaluation finding
8. Current or recurrent disease that could affect the results of the clinical or laboratory assessments required for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation between LF-PB exposures and efficacy after the administration of LF-PB 10 mg, 20 mg, and 30 mg	correlation between exposure of the drug and efficacy	12 weeks after surgery

Collaborators and Investigators

• Sponsor: Chemi S.p.A.
• Investigators: Principal Investigator: Paolo Carcoforo, MD, Clinica Chirurgica, Azienda Ospedaliero-Universitaria Arcispedale "S. Anna" Ferrara

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 12, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (Estimate): December 21, 2012

Study Record Updates

• Last Update Posted (Estimate): July 29, 2014
• Last Update Submitted That Met QC Criteria: July 28, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: LF-PB/11/04