Desmopressin (DDAVP) in Patients With Colorectal Cancer and Rectal Bleeding

Laboratorio Elea

Status and phase

Completed

Phase 2

Conditions

Rectal Bleeding

Colorectal Cancer

Treatments

Drug: Desmopressin

Study type

Interventional

Funder types

Industry

Identifiers

NCT01623206

DDAVP-R01-02

Details and patient eligibility

About

The objective of this study is to find the maximum tolerated dose and preliminary efficacy of desmopressin as an haemostatic agent, when is administered to patients with colorectal cancer and rectal bleeding, before specific oncologic treatment with surgery and/or chemotherapy and/or radiotherapy.

Full description

Colorectal cancer is the third cause of cancer in men and women, according to data recently published in the United Sates, and the third cause of death in the same population. Ninety percent (90%) of patients have symptoms at the time of diagnosis, being rectal bleeding the most frequent one (50% of cases). Bleeding, mainly mild or moderate, has no specific treatment, and during the staging of the disease, can not be controlled.

Desmopressin, a synthetic analogue of vasopressin, is a selective agonist of the receptor V2 of vasopressin, inducing, among others, an haemostatic effect. Interestingly, the expression of this receptor has been described in human gastrointestinal tract, including colon and rectum and in colorectal tumors. Moreover, desmopressin has shown a significant antitumor activity in preclinical murine models of colorectal cancer.

This is a dose finding study, to investigate a new indication of desmopressin as an haemostatic agent in patients with colorectal cancer with mild to moderate rectal bleeding.

Enrollment

30 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients > 18 to < 80 years of age who have signed the informed consent form
Histological diagnosis of rectal adenocarcinoma localized, locally advanced or metastatic
Treatment indication with chemotherapy and/or radiotherapy and/or surgery according to disease stage
Rectal bleeding associated with the primary tumor within 48 hours prior to study entry
Acceptable organ function to be able to participate in the study, performed within 14 days prior to admission; defined by the following parameters:
- Electrocardiogram (ECG) without significant clinical abnormalities
- Haemoglobin greater than or equal to 8 g/dL
- Total leukocyte count greater than or equal to 4.0 x 10^9/L
- Absolute neutrophil count greater than or equal to 1.5 x 10^9/L
- Total platelet count greater to 100.0 x 10^9/L
- Total bilirubin less than or equal to 1.5 times the upper limit of normality (ULN)
- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than or equal to 1.5 times upper limit of normality (ULN)
- Creatinine clearance greater than 50 ml/min
Performance status (Eastern Cooperative Oncology Group [ECOG]) less than or equal to 2
Patients with childbearing potential should use one of the following contraceptives methods: intrauterine devices, barrier methods and tubal ligation

Exclusion criteria

Colorectal cancer without bleeding evidences
Pregnancy or lactation
Use of hormonal contraceptives or treatments with sexual hormones in general
Patients with other illnesses not adequately controlled such as congestive heart failure, arterial blood pressure, unstable angina, severe cardiac arrhythmia, thromboembolic disease, diabetes 1 or 2, any hidden coronary disease determined by previous assessments
Psychiatric diseases implying patient incompetence
Known hypersensitivity to desmopressin or vasopressin
Severe von Willebrand disease (vWD)(defined by vWF<10% Ui/dl) or 2B vWD (defined by increased platelet agregation induced by ristocetin at low concentration) or hemophilia A or B carriers
History of seizures
Renal insufficiency (Creatinine clearance < 50 ml/min), hyponatremia (serum sodium lower than the lower limit of normality-UNL)or previous history of hyponatremia
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Positive serology for hepatitis B, C or known human immunodeficiency virus (HIV) infection
Known liver disease (cirrhosis, liver enzymes greater than or equal to 1.5 times the upper limit of normality or total bilirubin greater than or equal to 1.5 times the upper limit of normality
Active infections wich, according to the investigator judgement, coud interfere with patient safety
Other malignancies, with the exception of basal cell carcinoma, in situ cervical carcinoma, or any other tumour adequately treated and with a disease-free period greater than or equal to 5 years
Patients receiving or having received other investigational drugs 30 days prior to study entry