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

NCT01623206 | Completed Phase 2

• 1 other identifier: DDAVP-R01-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Colorectal Cancer; Rectal Bleeding

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to one week after the administration of the first dose

Secondary Outcomes (4)

• Number of patients with grade 3 or 4 local adverse events

  Up to one week after the administration of the first dose

• Number of patients with grade 3 or 4 systemic adverse events

  Up to one week after the administration of the first dose

• Number of withdrawn from treatment

  Up to one week after the administration of the first dose

• Number of patients with partial or complete response in clinical endpoints

  Up to one week after the administration of the first dose

Study Arms (1)

Desmopressin

EXPERIMENTAL

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

Drug: Desmopressin

Interventions

Desmopressin DRUG

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.

Desmopressin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Laboratorio Elea Phoenix S.A.: lead

Study Sites (2)

Hospital de Gastroenterologia ¨B.Udaondo¨

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1264AAA, Argentina

Location

Instituto de Oncología "Alexander Fleming"

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Location

Related Publications (1)

• 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.

  PMID: 32166534 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Gastrointestinal Hemorrhage

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Enrique Roca, MD

  Hospital de Gastroenterologia ¨B. Udaondo¨

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2012
• First Posted: June 19, 2012
• Study Start: April 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: August 1, 2017
• Last Updated: August 24, 2017

Record last verified: 2017-08

Locations

AR (2)