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Evaluation of the Effect of Pasireotide LAR Administration in the Lymphocele Prevention After Axillary Node Dissection for Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Evaluation of the Effect of Pasireotide LAR Administration in the Lymphocele Prevention After Axillary Node Dissection for Breast Cancer

Octreotide, a somatostatin analog, has demonstrated its efficacy in the medical management
of postoperative gastro-intestinal and pancreatic fistulae. Two recent studies have shown
its value in reducing lymphoceles following axillary node dissection performed as part of
breast cancer surgery.

The principal morbidity following axillary node dissection within the scope of breast cancer
surgery is the postoperative development of lymphocele following the removal of an axillary
drain. This may be a source of pain, repeated aspiration, infection and delayed local

Pasireotide, a somatostatin analog under evaluation and possessing a high affinity for
somatostatine receptors (30 to 40 times greater for sst1 and sst5 receptors, 5 times greater
for sst3 and equivalent for sst2) is an attractive molecule in this indication.

Based on the encouraging results published with octreotide and the greater effects
anticipated with pasireotide, the investigators want to assess the benefit of preoperative
administration of pasireotide in reducing the incidence of axillary lymphoceles following
mastectomy - axillary node dissection.

Somatostatin is a hormone that is widely distributed in the nervous and gastropancreatic
system responsible for a variety of pharmacological and physiological effects. It can
inhibit gastrointestinal endocrine and exocrine secretion and has an anti-inflammatory
action (1). The direct effect of somatostatin on lymphatic flow has only been observed on
the gastrointestinal tract.

Several series report the use of octreotide in the treatment of chylous ascites or in the
management of thoracic duct injury (2). Although its mechanism of action has not been
studied in depth, it probably acts by inhibiting splanchnic blood flow and limiting the
absorption of triglycerides.

Somatostatin receptors have been demonstrated in lymphatic tissues, including those not
associated with the intestinal tract. It is therefore probable that the inhibitory action of
somatostatin on gastrointestinal lymphatic flow may also apply elsewhere in the body, and to
the lymphatic system in particular.

Somatostatin might therefore decrease lymphatic flow following essentially axillary

A new molecule, pasireotide, is currently in clinical development. This molecule is a
somatostatin analog possessing an affinity 30 to 40 times greater for sst1 and sst5
receptors, 5 times greater for sst3 and comparable for sst2 than octreotide. It could
therefore have a greater effect than octreotide.

The gradual release form must be injected intramuscularly prior to surgery. An effective
plateau concentration is obtained after 10 days regardless of the selected dosage (20, 40,
or 60 mg).

In addition to the many articles in the literature detailing the beneficial effects of
octreotide on gastrointestinal and pancreatic fistulae and on regression of chylous ascites
and chylothorax, a few articles have attempted to highlight its effect on postoperative

Firstly, two articles have highlighted the positive effect of somatostatin analogs in
reducing drainage volume and the incidence of lymphoceles following axillary node dissection
in breast cancer:

Another more recent article by Mahmoud et al. (5) showed the same beneficial effects on the
mean daily drainage volume (104 vs 145 ml, p=0.0001), the total duration of drainage (12.7
vs 25 days, p=0.0001) and the need for postoperative aspiration of lymphoceles (90 vs 40%,

In 2006, in a different field (that of renal transplantation), an article by Capocasale et
al.Pasireotide is an injectable somatostatin analog. Like natural somatostatin and known
analogs, its pharmaceutical efficacy depends on its binding to somatostatin receptors. There
are five of these (sst 1 to 5); they are expressed in various bodily tissues under normal
physiological conditions. Somatostatin analogs activate these receptors, which in turn
reduce cell activity and inhibits hormone synthesis. (7). Octreotide and lanreotide, which
are currently used, have a strong affinity for the sst2 receptor and moderate affinity, if
any, for the other types. Pasireotide possesses greater affinity than octreotide for certain
somatostatin receptors: 30 times greater for sst1, 5 times greater for sst3 and 40 times
greater for sst5. It possesses equivalent affinity for sst2 and none (like octreotide) for

In the literature, the incidence of axillary lymphoceles following surgery for breast cancer
varies considerably: a recent meta-analysis of 66 studies revealed an incidence of 4 to 89 %
depending on whether or not drainage was being carried out, the type of surgery
(conservative or not), the time at which the drain was removed and whether or not a
compression dressing was applied.

In our experience, the incidence at Hôpital Tenon is 40%. This percentage has been
corroborated by Gustave Roussy Institute data, which recorded an incidence of 39.3% in out
of 70 patients who underwent surgery between November 2008 and February 2009.

Several teams have reported their use of Sandostatin® or other somatostatin analogs in the
management of patients suffering from inoperable peritoneal carcinoma (9-12). This treatment
was used as supportive therapy and reduced the incidence of symptoms associated with an
obstructive syndrome. It fact, it can reduce gastrointestinal secretions. Some authors have
even suggested that somatostatin analogs possess an anti-tumor effect (9). Octreotide is
recommended by AFSSAPS in the treatment of palliative care patients presenting with
intestinal occlusion in peritoneal carcinoma. Since a Marketing Authorization (MA) has been
granted for the use of somatostatin analogs in patients presenting with a gastrointestinal
endocrine tumor, the use of pasireotide does not raise any specific ethical issue.

Inclusion Criteria:

- Female patient aged 18 years or over.

- Patient understands French.

- Patient covered by the French national health insurance system.

- Any female patient scheduled for breast surgery with mastectomy and axillary node
dissection indicated at the pre-surgical stage.

Exclusion Criteria:

- Patient under the age of 18 years.

- Patient who does not understand French.

- Patient not covered by the French national health insurance system.

- Patient exhibiting one or more contraindications to anesthesia and surgery.

- Patient with a contra-indication to pasireotide

- Refusal by the patient

- Scheduled sentinel node procedure

- Abnormal coagulation or curative anticoagulant treatment

- Women of child-bearing potential without effective contraception,

- Pregnant or breast-feeding women

- Poorly controlled diabetes (HbA1c > 8%)

- History of radiotherapy

- Recurrent breast cancer

- Patient with a congestive cardiac insufficiency (NYHA category III or IV), an
instable angina pectoris, sustained ventricular tachycardia or ventricular
fibrillation episodes or history of myocardial infarction during the last 6 months.

- Patient presenting an extension of QT interval (QT corrected according to the
Fridericia formula (QTcF)) at the screening or baseline (predose) > 450msec

- History of syncope or family history of sudden death or significant cardiac

- Risk factors for torsades de pointes: hypokaliaemia, hypomagnesaemia, known
structural or ischaemic cardiac disease, bradycardia (HR<55/min) or high grade AV

- Concomitant disease that could prolong QT or increase exposure to the study
medication including dehydration, renal or hepatic impairment

- Concomitant medication known to increase the QT interval

- Patient with an hepatic pathology such as cirrhosis, chronic hepatitis active or
persistent, or an elevation of ALAT rate, ASAT rate twice higher than the normal
superior limit (NSL)

- Patient having leucocytes < 3x109/L, Hb < 90% LIN, platelets < 100x109/L

- Patient having a pathology or medical history susceptible to interfere with the
realization of the study or results evaluation according to the judgment of the
investigator or the study monitor

- Patient participating to another clinical trial with another molecule in study during
the month before the first dose

- Known oversensitivity to somatostatine analogs or another component of prolonged
release pasireotide or prolonged release octreotide formulations.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Outcome Measure:

aspirations global volume of lymphoceles

Outcome Description:

the patients ratio who did not have post-operative axillary symptomatic lymphoceles defined as the absence of aspiration or a unique or iterative aspirations global volume of lymphoceles inferior to 60cc inclusive (≤) in the 28 days after the intervention or a systematic aspiration volume at the 28th day inferior to 120cc inclusive (≤).

Outcome Time Frame:

1 to 32 days after surgery

Safety Issue:



France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

September 2010

Completion Date:

July 2012

Related Keywords:

  • Breast Cancer
  • mastectomy
  • axillary node dissection
  • adjuvant or neoadjuvant
  • Breast Neoplasms
  • Lymphocele