Perioperative Use of Desmopressin (DDAVP) in Breast Cancer

Perioperative Administration of Desmopressin to Subjects With Breast Cancer: A Phase IIa, Dose-Escalation Study

The propose for this study is to evaluate the safety and tolerability of desmopressin when administered perioperatively to patients with breast cancer undergoing surgery as first treatment, and select the optimum dose for the clinical development of the product.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Desmopressin

Detailed Description

Breast cancer is one of the most commonly diagnosed malignancies among women, and its mortality is related to the capacity of tumor cells to invade and produce metastases. It is postulated that tumor manipulation during surgery results in the release of tumor cells into circulation or the lymphatic system, and that these released cells survive due to aggregation among them or with platelets through the formation of a fibrin layer on the embolus. Tumor cells surviving transportation through circulation will join blood vessels and invade vascular walls, forming metastases. The interruption of this process might reduce survival of tumor cells and thus the formation of metastases from breast cancer cells in the lungs or other tissues.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Interzonal General De Agudos EvaPeron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• a. Female subjects from 21 to 60 years of age, who have voluntarily signed the informed consent form.

  b. Histological/cytological diagnosis of breast carcinoma obtained at least 21 days before inclusion into the study.

  c. Candidate for radical mastectomy and requiring resection of axillary lymph nodes or sentinel node.

  d. In case of women of childbearing potential, an adequate birth control method (intrauterine device, barrier methods, or tubal ligation) should be used throughout the study. Post-menopausal women should have menopause confirmed by biochemical parameters.

  e. Adequate organic function, defined by the following parameters:

  • Electrocardiogram (ECG) with no significant anomalies, performed within 14 days prior to surgery.
  • The following laboratory results, obtained 7 days before surgery:
  • Hemoglobin ≥ 11 g/dL
  • Total white blood cell count ≥ 4,000/mm3
  • Total neutrophil count 1,500/mm3
  • Platelet count within normal limits
  • Total bilirubin ≤1.5 x UNL or 2.5 x UNL in case of hepatic metastasis
  • Transaminases ALT/GPT and AST/GOT ≤ 1.5 x UNL
  • Creatinine clearance >50 mg/dL

  • CT scan with oral and endovenous contrast* of chest, pelvis, and abdomen, and bone scan, conducted within 28 days prior to surgery. Images taken not longer than 90 days before surgery are also acceptable.

    • In case contrast is contraindicated, CT with no contrast or MRI will be performed.

      f. Subject with performance status (ECOG) = 0.

Exclusion Criteria:

• a. Synchronic bilateral breast cancer. b. Symptoms of metastasis or evidence of metastasis from images: chest spiral CT scan, abdomen/pelvis spiral CT scan, brain spiral CT/MRI (in case of brain metastasis signs), and bone scan.

  c. The patient is pregnant or breastfeeding. d. The patient is presently using hormonal contraceptives or under hormonal treatment. She would be eligible if oral contraceptives were discontinued or if the hormonal treatment finished 30 days before surgery and the patient agreed to use another contraceptive method.

  e. Patients with a history or presence of congestive heart failure, blood hypertension, angina pectoris or heart arrhythmia, thromboembolic disease, diabetes type I or II, or any underlying coronaropathy detected in pre-surgical evaluations.

  f. Mentally-impaired patients. g. Patients with known hypersensitivity to DDAVP or vasopressin, o with severe von Willebrand's disease (VWD), defined by a VWF activity <10%IU/dL, or type 2B VWD, defined by an increased ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin or with hemophilia.

  h. Patients with a history of seizures. i. Patients with renal impairment (creatinine clearance < 50 mL/min calculated by the Cockcroft-Gault formula), hyponatremia or with a history of hyponatremia.

  j. Patients with syndrome of inadequate secretion of antidiuretic hormone. k. Patients with positive serology for the hepatitis B or C virus and/or HIV. l. Patients with known hepatic disease (diagnosed cirrhosis, hepatic enzymes (GOT/GPT) > 1.5 x UNL, Total bilirubin > 1.5 x UNL).

  m. Patients with active infections. n. Patients with other malignant diseases, with the exception of, non-melanoma skin cancer, or cervix cancer in situ, or any other tumor that has received adequate treatment and shows a disease-free time ≥ 5 years.

  o. Patients participating in another clinical study or cases in which less than 4 weeks have elapsed since participation in another clinical study.

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Desmopressin	Drug: Desmopressin; 20 patients in 5 groups 4 each, advancing progressively to each dose level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Selection of the higher safe dose level for ensuing clinical trials	One of the three dose levels assessed in this study will be selected for further clinical testing in adults: 0,50 mg, 1,0 mg, 1,25 mg, 1,5 mg or 2,0 mg.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Evidence of V2 Receptor Expression	Baseline
Evidence of CTC (CIRCULATING TUMOR CELLS)	Baseline
Evidence of Von Willebrand factor antigen (VWF:Ag)	Baseline
Evidence of CTC (circulating tumor cells)	30 minutes pre surgery and 24 hours post the surgery
Evidence of CTC (circulating tumor cells)	2 Weeks
Evidence of CTC (circulating tumor cells)	1 Month
Evidence of CTC (circulating tumor cells)	3 Months
Evidence of CTC (circulating tumor cells)	6 Months
Evidence of CTC (circulating tumor cells)	12 Months
Evidence of Von Willebrand factor antigen (VWF:Ag)	120 minutes post the surgery
Evidence of VWF activity (ristocetin cofactor, VWF:RCo)	baseline
Evidence of VWF activity (ristocetin cofactor, VWF:RCo)	120 minutes post the surgery
Evidence of FVIII coagulant activity (FVIII:C)	baseline
Evidence of FVIII coagulant activity (FVIII:C)	120 minutes post the surgery
Evidence of euglobulin lysis time	baseline
Evidence of euglobulin lysis time	120 minutes post the surgery

Collaborators and Investigators

• Sponsor: Laboratorio Elea Phoenix S.A.
• Investigators: Principal Investigator: Dra. Ruth Weinberg, Hospital Interzonal General de Agudos Eva Perón

Publications and helpful links

General Publications

• Weinberg RS, Grecco MO, Ferro GS, Seigelshifer DJ, Perroni NV, Terrier FJ, Sanchez-Luceros A, Maronna E, Sanchez-Marull R, Frahm I, Guthmann MD, Di Leo D, Spitzer E, Ciccia GN, Garona J, Pifano M, Torbidoni AV, Gomez DE, Ripoll GV, Gomez RE, Demarco IA, Alonso DF. A phase II dose-escalation trial of perioperative desmopressin (1-desamino-8-d-arginine vasopressin) in breast cancer patients. Springerplus. 2015 Aug 19;4:428. doi: 10.1186/s40064-015-1217-y. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: May 11, 2012
• First Submitted That Met QC Criteria: May 23, 2012
• First Posted (ESTIMATE): May 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 28, 2015
• Last Update Submitted That Met QC Criteria: August 27, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: DDAVP
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: DDAVP