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

Primary Purpose

Colorectal Cancer, Rectal Bleeding

Status
Completed
Phase
Phase 2
Locations
Argentina
Study Type
Interventional
Intervention
Desmopressin
Sponsored by
Laboratorio Elea Phoenix S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Colorectal Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Hospital de Gastroenterologia ¨B.Udaondo¨
  • Instituto de Oncología "Alexander Fleming"

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Desmopressin

Arm Description

Four dose levels and two dosing schedules with 3 patients in each group.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Number of patients with grade 3 or 4 local adverse events
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.
Number of patients with grade 3 or 4 systemic adverse events
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.
Number of withdrawn from treatment
Number of patients with partial or complete response in clinical endpoints
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.

Full Information

First Posted
May 28, 2012
Last Updated
August 23, 2017
Sponsor
Laboratorio Elea Phoenix S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT01623206
Brief Title
Desmopressin (DDAVP) in Patients With Colorectal Cancer and Rectal Bleeding
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Laboratorio Elea Phoenix S.A.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Rectal Bleeding

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Desmopressin
Arm Type
Experimental
Arm Description
Four dose levels and two dosing schedules with 3 patients in each group.
Intervention Type
Drug
Intervention Name(s)
Desmopressin
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
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 tolerated dose.
Time Frame
Up to one week after the administration of the first dose
Secondary Outcome Measure Information:
Title
Number of patients with grade 3 or 4 local adverse events
Description
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.
Time Frame
Up to one week after the administration of the first dose
Title
Number of patients with grade 3 or 4 systemic adverse events
Description
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.
Time Frame
Up to one week after the administration of the first dose
Title
Number of withdrawn from treatment
Time Frame
Up to one week after the administration of the first dose
Title
Number of patients with partial or complete response in clinical endpoints
Description
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.
Time Frame
Up to one week after the administration of the first dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrique Roca, MD
Organizational Affiliation
Hospital de Gastroenterologia ¨B. Udaondo¨
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Gastroenterologia ¨B.Udaondo¨
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1264AAA
Country
Argentina
Facility Name
Instituto de Oncología "Alexander Fleming"
City
Ciudad Autónoma de Buenos Aires
State/Province
Buenos Aires
Country
Argentina

12. IPD Sharing Statement

Citations:
PubMed Identifier
32166534
Citation
Iseas S, Roca EL, O'Connor JM, Eleta M, Sanchez-Luceros A, Di Leo D, Tinelli M, Fara ML, Spitzer E, Demarco IA, Ripoll GV, Pifano M, Garona J, Alonso DF. Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial. Invest New Drugs. 2020 Oct;38(5):1580-1587. doi: 10.1007/s10637-020-00914-5. Epub 2020 Mar 12.
Results Reference
derived

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

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