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Study of Individualized Therapies Selection for Patients With Metastatic Colorectal Carcinoma According to the Therapeutic

Primary Purpose

Adenocarcinoma of Colon, Adenocarcinoma of Rectum, Metastatic Disease

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Arm A chemotherapy
arm B chemotherapy
Sponsored by
Centro Nacional de Investigaciones Oncologicas CARLOS III
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of Colon focused on measuring Genomic expression profile in tumor samples, Adult patients, metastatic disease status and progression after two lines of systemic therapy

Eligibility Criteria

18 Years - 76 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histological examination showed of metastatic colon carcinoma.
  • Patients more than 18 years.
  • Measurable disease according to RECIST 1.1 criteriso
  • Life expectancymore than 3 months according to the criteria of the investigator.
  • Goodoverall condition determined by the ECOG scale (score 0-1)
  • Candidate for systemic treatment based on the profile of sensibility to drugs determined by genetic analysis of the tumor sample. Patients should have received at least two lines of standard treatment, including therapies antiEGFR in cases of tumors with Kras oncogene B-Raf and native (non-mutated).
  • Availability of tumor tissue or potential for tumor biopsy correlation allowing the RNA expression profile with that obtained from the peripheral blood CTCs.
  • Adequate hematologic function: ANCmore than 1.5 x 103 / L, platelet count absolute more than 100 x 109 / L, normal values of INR and PTT.
  • Adequate liver function: total serum bilirubin no more than 2 mg / dL, ALT and AST no more than 3 times the upper limit established by the laboratory (LSR) or no more than 5 LSR in patients with liver metastases.
  • Adequate renal function: serum creatinine no more than 1.5 LSR or calculated creatinine clearance 60 ml / min (Crock).

Exclusion Criteria:

  • The patient has received systemic cancer treatment within two weeks prior to extraction of the blood sample.
  • Patient has received therapeutic radioisotopes such as strontium 89 within 4 weeks before blood extraction.
  • Patient has had major surgery or percutaneous procedures such as placement of central venous catheter within 2 weeks prior to the blood draw.
  • Patient has a history as bone marrow transplantation and / or stem cell transplantation.
  • Patient has any of the following concomitant diseases or current conditions:

chronic active liver disease of any origin, and / or cirrhosis with Child-Pugh score B or C.

Uncontrolled active infection. carries the human immunodeficiency virus (HIV). Any other significant disease that in the opinion of the investigator, substantially increase the risk associated with patient participation in this study.

documented symptomatic brain metastases, progression or requiring corticosteroids or associated to a leptomeningeal involvement.

Patients with uncontrolled systemic diseases. Patients with Hypertension or Diabetes Mellitus is countable if at the time of inclusion deemed medically controlled.

Patients with inability for oral drug delivery, either by preventing gastrointestinal administration situation or severe impairment of intestinal absorption

  • Any medical or psychiatric condition that, in the opinion of the investigator, may limit the patient's ability to understand and fulfill all requirements under its partcipación in the study.
  • Pregnant or lactating women

Sites / Locations

  • Hospital Universitario de Fuenlabrada
  • Hospital Madrid Norte Sanchinarro

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm Description

Control treatment and will be treated with any of the schemes used in the study according to the discretion of the physician.

Treatment guided by the gene expression profiles obtained from the CTC

Outcomes

Primary Outcome Measures

Overall survival
To determine the tumor progression-free survival at 3 and 6 months (PFS3 and PFS6) in both groups of patients and identify whether there is a statistically significant difference
gene expression profiles
Assess the correlation between the gene expression profiles obtained from the CTC and the gene expression profiles obtained from tumor samples from the same patients.

Secondary Outcome Measures

Full Information

First Posted
October 8, 2012
Last Updated
October 8, 2015
Sponsor
Centro Nacional de Investigaciones Oncologicas CARLOS III
Collaborators
Hospital Universitario de Fuenlabrada, Grupo Hospital de Madrid, Apices Soluciones S.L.
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1. Study Identification

Unique Protocol Identification Number
NCT01703910
Brief Title
Study of Individualized Therapies Selection for Patients With Metastatic Colorectal Carcinoma According to the Therapeutic
Official Title
Phase II Individualized Therapies Selection Study for Patients With Metastatic Colorectal Carcinoma According to the Genomic Expression Profile in Tumor Samples.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centro Nacional de Investigaciones Oncologicas CARLOS III
Collaborators
Hospital Universitario de Fuenlabrada, Grupo Hospital de Madrid, Apices Soluciones S.L.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the feasibility of selecting personalized therapies for colon cancer patients who have failed standard treatments, using a new methodology based on the determination of a profile of chemosensitivity by comprehensive genetic expression analysis from tumor samples.
Detailed Description
It is a prospective, randomized study in patients with metastatic colorectal carcinoma progressing after two lines of prior therapy. Patients will be randomized (1:1) to receive chemotherapy as determined by its oncologist or treatment according to chemosensitivity profile obtained. For obtaining the profile a histological tumor sample and a sample of venous blood in a tube with heparin standard are necessary . This latter sample will be processed to isolate circulating tumor cells by cell adhesion with matrix coated glass spheres. The RNA from these circulating tumor cells as well as from tumor cells of tumor biopsies from the same patients will be extracted by a standard procedure for extracting RNA for genetic expression analysis. Based on the analysis performed on tumor biopsy is generated a ranked list of potentially more effective treatments in every case

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of Colon, Adenocarcinoma of Rectum, Metastatic Disease
Keywords
Genomic expression profile in tumor samples, Adult patients, metastatic disease status and progression after two lines of systemic therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
Control treatment and will be treated with any of the schemes used in the study according to the discretion of the physician.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Treatment guided by the gene expression profiles obtained from the CTC
Intervention Type
Drug
Intervention Name(s)
Arm A chemotherapy
Other Intervention Name(s)
Capecitabine, Cisplatin, Cetuximab, Doxorubicin, Fluorouracil, Gemcitabine, Irinotecan, Topotecan, Mitomycin C, Oxaliplatin, Paclitaxel, Docetaxel, Pemetrexed, Raltitrexed, Sorafenib, Erlotinib, Vinorelbine, Dasatinib, Etoposide
Intervention Type
Drug
Intervention Name(s)
arm B chemotherapy
Other Intervention Name(s)
Capecitabine, Cisplatin, Cetuximab, Doxorubicin, Fluorouracil, Gemcitabine, Irinotecan, Topotecan, Mitomycin C, Oxaliplatin, Paclitaxel, Docetaxel, Pemetrexed, Raltitrexed, Sorafenib, Erlotinib, Vinorelbine, Dasatinib, Etoposide
Primary Outcome Measure Information:
Title
Overall survival
Description
To determine the tumor progression-free survival at 3 and 6 months (PFS3 and PFS6) in both groups of patients and identify whether there is a statistically significant difference
Time Frame
12 months
Title
gene expression profiles
Description
Assess the correlation between the gene expression profiles obtained from the CTC and the gene expression profiles obtained from tumor samples from the same patients.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
76 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological examination showed of metastatic colon carcinoma. Patients more than 18 years. Measurable disease according to RECIST 1.1 criteriso Life expectancymore than 3 months according to the criteria of the investigator. Goodoverall condition determined by the ECOG scale (score 0-1) Candidate for systemic treatment based on the profile of sensibility to drugs determined by genetic analysis of the tumor sample. Patients should have received at least two lines of standard treatment, including therapies antiEGFR in cases of tumors with Kras oncogene B-Raf and native (non-mutated). Availability of tumor tissue or potential for tumor biopsy correlation allowing the RNA expression profile with that obtained from the peripheral blood CTCs. Adequate hematologic function: ANCmore than 1.5 x 103 / L, platelet count absolute more than 100 x 109 / L, normal values of INR and PTT. Adequate liver function: total serum bilirubin no more than 2 mg / dL, ALT and AST no more than 3 times the upper limit established by the laboratory (LSR) or no more than 5 LSR in patients with liver metastases. Adequate renal function: serum creatinine no more than 1.5 LSR or calculated creatinine clearance 60 ml / min (Crock). Exclusion Criteria: The patient has received systemic cancer treatment within two weeks prior to extraction of the blood sample. Patient has received therapeutic radioisotopes such as strontium 89 within 4 weeks before blood extraction. Patient has had major surgery or percutaneous procedures such as placement of central venous catheter within 2 weeks prior to the blood draw. Patient has a history as bone marrow transplantation and / or stem cell transplantation. Patient has any of the following concomitant diseases or current conditions: chronic active liver disease of any origin, and / or cirrhosis with Child-Pugh score B or C. Uncontrolled active infection. carries the human immunodeficiency virus (HIV). Any other significant disease that in the opinion of the investigator, substantially increase the risk associated with patient participation in this study. documented symptomatic brain metastases, progression or requiring corticosteroids or associated to a leptomeningeal involvement. Patients with uncontrolled systemic diseases. Patients with Hypertension or Diabetes Mellitus is countable if at the time of inclusion deemed medically controlled. Patients with inability for oral drug delivery, either by preventing gastrointestinal administration situation or severe impairment of intestinal absorption Any medical or psychiatric condition that, in the opinion of the investigator, may limit the patient's ability to understand and fulfill all requirements under its partcipación in the study. Pregnant or lactating women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Gómez, M.D.,Ph.D
Organizational Affiliation
Centro Nacional de Investigaciones Oncológicas (CNIO)
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Universitario de Fuenlabrada
City
Fuenlabrada
State/Province
Madrid
ZIP/Postal Code
28950
Country
Spain
Facility Name
Hospital Madrid Norte Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain

12. IPD Sharing Statement

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Study of Individualized Therapies Selection for Patients With Metastatic Colorectal Carcinoma According to the Therapeutic

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