Prospective, Open-labelled, Phase II Study, of the Administration of Desmopressin in Patients With Colorectal Cancer, With or Without Metastasis, With Rectal Bleeding, Before Treatment With Surgery and/or Chemotherapy and/or Radiotherapy.
18 Years
80 Years
Both
Colorectal Cancer, Rectal Bleeding
Trial Information
Prospective, Open-labelled, Phase II Study, of the Administration of Desmopressin in Patients With Colorectal Cancer, With or Without Metastasis, With Rectal Bleeding, Before Treatment With Surgery and/or Chemotherapy and/or Radiotherapy.
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Outcome Measure:
Presence or absence of grade 3 or 4 adverse events related to the study drug, in a maximum of 2 out of 6 patients assessed in each dose level.
Outcome Description:
A total of 6 groups with 3 patients each, with different dose ranges and dosing schedules will be assessed. The number of patients in each group with grade 3 or 4 adverse events, including clinical or analytical findings, will be determined in order to stablish the maximum torerated dose.
Outcome Time Frame:
Up to one week after the administration of the first dose
Safety Issue:
Yes
Principal Investigator
Enrique Roca, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hospital de Gastroenterologia ¨B. Udaondo¨
Authority:
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Study ID:
DDAVP-R01-02
NCT ID:
NCT01623206
Start Date:
October 2012
Completion Date:
June 2013
Related Keywords:
- Colorectal Cancer
- Rectal Bleeding
- Colorectal Neoplasms
- Hemorrhage
- Gastrointestinal Hemorrhage
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