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

August 23, 2017 updated by: Laboratorio Elea Phoenix S.A.

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.

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.

Study Overview

Status

Completed

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1264AAA
        • Hospital de Gastroenterologia ¨B.Udaondo¨
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
        • Instituto de Oncología "Alexander Fleming"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Desmopressin
Four dose levels and two dosing schedules with 3 patients in each group.

Dose groups: Group 1: 0.25 µg/kg/day; Group 2: 0.25 µg/kg/12 hours; Group 3: 0.50 µg/kg/12 hours; Group 4: 1 µg/kg/day; Group 5: 1 µg/kg/12 hours; Group 6: 2 µg/kg/day.

All groups will receive desmopressin intravenously, in a 15-20 minutes infusion, one or two times a day. The administration will be repeated 24 hours after the first infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Up to one week after the administration of the first dose

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 tolerated dose.

Up to one week after the administration of the first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with grade 3 or 4 local adverse events
Time Frame: Up to one week after the administration of the first dose
Once the maximum tolerated dose is determined, other 12 patients will be assessed to evaluate safety and tolerability of the study drug when administered as monotherapy.
Up to one week after the administration of the first dose
Number of patients with grade 3 or 4 systemic adverse events
Time Frame: Up to one week after the administration of the first dose
Once the maximum tolerated dose is determined, other 12 patients will be assessed to evaluate safety and tolerability of the study drug when administered as monotherapy.
Up to one week after the administration of the first dose
Number of withdrawn from treatment
Time Frame: Up to one week after the administration of the first dose
Up to one week after the administration of the first dose
Number of patients with partial or complete response in clinical endpoints
Time Frame: Up to one week after the administration of the first dose

Clinical endpoints such us rectal bleeding, mucorrhea, evacuatory attempts and rectal pain will be assessed before and after treatment with the study drug.

Response will be classified as complete or partial response.

Up to one week after the administration of the first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Enrique Roca, MD, Hospital de Gastroenterologia ¨B. Udaondo¨

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

July 1, 2017

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

May 28, 2012

First Submitted That Met QC Criteria

June 15, 2012

First Posted (Estimate)

June 19, 2012

Study Record Updates

Last Update Posted (Actual)

August 24, 2017

Last Update Submitted That Met QC Criteria

August 23, 2017

Last Verified

August 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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