Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Once the patient is asleep under anesthetic, they receive an intraoperative injection of 1.0 mCi of Technetium-99 sulfur colloid into normal breast tissue surrounding the primary cancer or biopsy cavity directed subareolar or around the tumor. This is followed by blue dye injected in the subareolar complex approximately 5 minutes prior to incision. The sentinel node biopsy is performed, followed by lumpectomy/mastectomy, and a completion axillary node dissection if the sentinel node(s) were positive.

Sentinel Node Biopsy

V. Suzanne Klimberg, MD

We continue to collect information in support of the hypothesis that the histology of the first draining lymph node (sentinel node) accurately predicts the histology of the rest of the axillary lymph nodes.

Using a technique combining Technetium-99 sulfur colloid and Lymphazurin Blue Dye, we have established that the sentinel node predicts the pathology results of the rest of the axillary lymph nodes. This minimally invasive technique, which can be readily performed under local anesthesia, makes the need for full axillary lymph node dissection unnecessary for most patients. If the sentinel node is negative, no further surgery is necessary. If positive, a complete axillary node dissection is performed. In addition, the injections are made while the patient is under anesthesia, reducing the physical and psychological pain that accompanies injections done pre-operatively.

Sentinel Lymph Node Biopsy Using Peritumoral Injection With Blue Dye Confirmation

University of Arkansas

Symptoms and General Pathology

Pathologic Complete Response

Breast Diseases

Skin Diseases

Disease Progression

Disease Attributes

Omit breast radiation for 3 years after surgery

Omit breast radiation

Armando Giuliano, MD, FACS, FRCSEd

The purpose of this study is to evaluate the feasibility, based on recruitment rate over a 3-year period, of enrolling patients for the omission of post-operative breast radiation following breast conserving surgery and sentinel node biopsy or axillary lymph node dissection in women with HER2+ breast cancer who achieve pathologic complete response.

Radiation Omission in Patients With HER2 Overexpressing Tumors With Pathologic Complete Response

Radiation Omission in Patients With HER2 Overexpressing Tumors With Pathologic

Measured by the number of recruited patients over the number of patients approached to participate to the trial. Feasibility will be defined as recruitment rate of greater or equal to 25% among patients who are eligible to participate in the trial.

Armando Giuliano

Chief, Surgical Oncology

Blood and Lymph Conditions

Lymphocele

Cysts

Lymphatic Diseases

Pasireotide

Hormones

Hormone Antagonists

INTRAMUSCULAR INJECTION OF PASIREOTIDE 60 MG

One INTRAMUSCULAR INECTION OF PASIREOTIDE 60 MG 10 TO 7 DAYS BEFORE SURGERY

PASIREOTIDE

ONE INJECTION OF PLACEBO 10 TO 7 DAYS BEFORE SURGERY

PLACEBO

The principal morbidity following axillary node dissection within the scope of breast cancer surgery is the post-operative development of lymphocele. According to the literature, incidence can vary from 4 to 89% depending on the type of surgery, whether or not a drain is inserted or a compression dressing applied and the time at which the drain is removed... In our experience, the incidence is 40% \[IGR (Gustave Roussy Institute) data focusing on 70 patients between November 2008 and February 2009\]

Encouraging results in terms of reducing postoperative lymphoceles as well as drainage duration and volume using Octreotide have been recorded in two recent studies. A new molecule developed by Novartis Laboratories, namely pasireotide, is a somatostatin analog possessing strong affinity for several somatostatin receptors (30 to 40 times greater for sst1 and sst5, 5 times greater for sst3 and equivalent for sst2)

The purpose of this trial is to assess the efficacy of a pre-surgical injection of pasireotide LAR in reducing the postoperative incidence of symptomatic lymphoceles following axillary node dissection.

The secondary objectives are to assess the efficacy of prolonged release pasireotide on the duration of postoperative drainage, the daily drainage volume, the total drainage volume, the number of repeated lymphocele aspirations and the volume, the total volume of lymph aspirated, the incidence of postoperative febrile episodes, the length of hospital stay, and the length of time to onset of adjuvant chemotherapy. It is also to assess the safety of prolonged release pasireotide.

The primary objective of this study is to assess the efficacy of a preoperative prolonged release pasireotide injection in the reduction in the incidence of symptomatic, postoperative axillary lymphoceles following mastectomy-axillary node dissection.

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 healing.

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 lymphadenectomy.

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 lymphoceles.

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%, p=0.0001).

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 sst4.

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.

Pasireotide LAR Administration in Lymphocele Prevention After Axillary Node Dissection for Breast Cancer

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

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 (≤).

Alliance Pour La Recherche en Cancerologie

Rare Diseases

Melanoma

Seroma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

Coagulants

Fibrin Tissue Adhesive

Hemostatics

Tisseel applied externally to the dissected axillary area.

Fibrin Sealant

Paul F. Mansfield, MD

Primary Objective:

* To determine whether the use of a fibrin sealant applied to axillary soft tissues following node dissection can result in earlier drain removal.

Secondary Objectives:

* To determine the postoperative morbidity rate using fibrin sealant following axillary node dissection.
* To assess patient-valuation of outcome by performing a cost-benefit analysis using a willingness-to-pay model.
* To determine if serum levels, lymphatic fluids level, or cutaneous expression of vascular endothelial growth factor-D (VEGF-D), vascular endothelial growth factor-C (VEGF-C) or their receptor, vascular endothelial growth factor receptor-3 (VEGFR-3) correlates with nodal tumor burden or development of lymphedema in patients with melanoma.

Patients in this study are scheduled to have axillary node dissection as part of their surgery for treatment of their melanoma.

Within 2 weeks before entry into the study, patients will have a complete physical exam and medical history.

These patients will be randomly assigned (as in the toss of a coin) to one of two groups. Patients in one group will receive TISSEEL applied externally to the dissected axillary area. Patients in the other group will receive no fibrin sealant.

For patients who are admitted to the hospital, the surgical site will be monitored by the surgeon for evidence of wound complications in the first 24 hours after surgery. At the time of discharge from the hospital, patients will be instructed in drain care and how to measure the drainage each day until the drain is removed.

The contents of the drain will be collected from patients during the first day after surgery, during the first return follow-up visit to M.D. Anderson Cancer Center, and during drain removal (unless these latter 2 dates are the same).

Follow-up wound exams will be performed by the local primary physician or in the M.D. Anderson Melanoma Clinic between 1-4 weeks and 6 weeks after surgery. Participation will be over at the 6-week follow-up.

THIS IS AN INVESTIGATIONAL STUDY. The sealant is FDA approved, though its use in this study is experimental. About 115 patients will take part in this study. All will be enrolled at M. D. Anderson.

Fibrin Melanoma Axillary Node Study in Patients With Melanoma

A Randomized Trial Evaluating the Use of Fibrin Tissue Adhesive Following Axillary Node Dissection in Patients With Melanoma

Number of participants with any signs of infection noted following surgery requiring intervention.

M.D. Anderson Cancer Center

No data collected for the Questionnaire Only Arm, therefore no adverse events to report for the Questionnaire Only Arm.

Tisseel applied externally to the dissected axillary area. Intervention: Drug: Fibrin Sealant

Treatment Arm

Control Arm

Questionnaire Only

Total

Baseline characteristics not taken for the questionnaire only arm.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Paul F Mansfield, Professor, Surgical Oncology

Data not collected for Questionnaire Only Arm.

Drain Duration

No data collected for Questionnaire Only Arm.

Number of Participants With Infection

Overall Study

Lymphedema

Neuroma

Technetium Tc 99m Sulfur Colloid

During surgery, the technetium-99m sulfur colloid will be injected into the breast and the blue dye injected (if the patient is not allergic and it is not required to locate the SLN) in the patient's ipsilateral upper arm. The lymph node biopsy and/or dissection will be performed by the surgeon, according to standard practice.

Axillary Reverse Mapping

Daniela Ochoa, MD

We hypothesize that variations in anatomic location of the arm lymphatic drainage system put the arm lymphatics at risk for disruption during a SLNB and / or ALND. Therefore, mapping the drainage of the arm during the procedure would decrease the likelihood of inadvertent disruption of the lymphatics and the subsequent development of lymphedema. A combination of radioactivity and blue dye will be used.

Mapping Procedure:

Each patient will receive an injection of 1.0 mCi of technetium-99m sulfur colloid into the normal breast tissue surrounding the primary cancer or biopsy cavity directed subareolar or around the tumor.

If the radioactive SLN cannot be located prior to incision via gamma probe then the blue dye will be used in the breast either in the subareolar plexus or peritumorally at the discretion of the surgeon. For this contingency (expected to occur \<3% of the time), the blue dye will be used in the breast (and NOT the arm), as the prime concern is locating the SLN for staging.

If the blue dye is unnecessary to find the sentinel node draining from the breast, then it will be injected dermally in the upper inner arm along the Biceps groove of the ipsilateral arm in order to locate the draining lymphatics from the arm. No more than 5cc of blue dye will be injected in either the subareolar plexus, peritumorally (intraparenchymal or dermally), or dermally in the patient's ipsilateral arm dependent upon the contingencies stated above. Site of all injections (radioactivity and/or blue dye) will be recorded.

ARM: Axillary Reverse Mapping, A Prospective Study

An occurrence will consist of an increase of 20% or more in ipsilateral arm volume over the pre-surgery volume, and be accompanied by a confirmatory diagnosis of lymphedema from the UAMS lymphedema clinic.

successful localization of one or more lymph nodes to which the peritumoral breast region drains

brief location details will also be collected.

successful avoidance of resection and/or successful preservation of structural integrity of arm lymphatics during the surgical procedure.

A crossover event will consist of identification of one or more lymph nodes that are both focally radioactive following peritumoral Tc99m injection and noticeably stained blue following ipsilateral arm injection with Lymphazurin.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sentinel Lymph Node Biopsy Using Peritumoral Injection With Blue Dye Confirmation	NCT00575744	Breast Cancer	Sentinel Node B...	18 Years -	University of Arkansas
Radiation Omission in Patients With HER2 Overexpressing Tumors With Pathologic Complete Response	NCT05371860	Breast Cancer HER2-positive B...	Omit breast rad...	40 Years -	Cedars-Sinai Medical Center
Pasireotide LAR Administration in Lymphocele Prevention After Axillary Node Dissection for Breast Cancer	NCT01356862	Breast Cancer	PASIREOTIDE PLACEBO	18 Years -	Alliance Pour La Recherche en Cancerologie
Fibrin Melanoma Axillary Node Study in Patients With Melanoma	NCT00504582	Melanoma	Fibrin Sealant	18 Years -	M.D. Anderson Cancer Center
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Sentinel Lymph Node Biopsy Using Peritumoral Injection With Blue Dye Confirmation	NCT00575744	Breast Cancer	Sentinel Node B...	18 Years -	University of Arkansas
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas
Axillary Reverse Mapping	NCT00572481	Cancer of the B...	Axillary Revers...	18 Years -	University of Arkansas

Spots Global Cancer Trial Database for axillary node dissection