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

Phase II Individualized Therapies Selection Study for Patients With Metastatic Colorectal Carcinoma According to the Genomic Expression Profile in Tumor Samples.

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Disease; Adenocarcinoma of Rectum; Adenocarcinoma of Colon
• Intervention / Treatment: Drug: Arm A chemotherapy; Drug: arm B chemotherapy

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

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28050
    • Hospital Madrid Norte Sanchinarro
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28950
      • Hospital Universitario de Fuenlabrada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Control treatment and will be treated with any of the schemes used in the study according to the discretion of the physician.	Drug: Arm A chemotherapy; Other Names: Gemcitabine; Cisplatin; Capecitabine; Irinotecan; Oxaliplatin; Doxorubicin; Topotecan; Etoposide; Fluorouracil; Docetaxel; Paclitaxel; Sorafenib; Vinorelbine; Cetuximab; Mitomycin C; Pemetrexed; Erlotinib; Dasatinib; Raltitrexed
Experimental: Arm B; Treatment guided by the gene expression profiles obtained from the CTC	Drug: arm B chemotherapy; Other Names: Gemcitabine; Cisplatin; Capecitabine; Irinotecan; Oxaliplatin; Doxorubicin; Topotecan; Etoposide; Fluorouracil; Docetaxel; Paclitaxel; Sorafenib; Vinorelbine; Cetuximab; Mitomycin C; Pemetrexed; Erlotinib; Dasatinib; Raltitrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months
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.	12 months

Collaborators and Investigators

• Sponsor: Centro Nacional de Investigaciones Oncologicas CARLOS III
• Collaborators: Apices Soluciones S.L.; Hospital Universitario de Fuenlabrada; Grupo Hospital de Madrid
• Investigators: Study Director: Carlos Gómez, M.D.,Ph.D, Centro Nacional de Investigaciones Oncológicas (CNIO)

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 8, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 11, 2012

Study Record Updates

• Last Update Posted (Estimate): October 9, 2015
• Last Update Submitted That Met QC Criteria: October 8, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Adult patients; Genomic expression profile in tumor samples; metastatic disease status and progression after two lines of systemic therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Folic Acid Antagonists; Gemcitabine; Docetaxel; Etoposide; Etoposide phosphate; Paclitaxel; Erlotinib Hydrochloride; Cisplatin; Fluorouracil; Sorafenib; Capecitabine; Oxaliplatin; Irinotecan; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin; Vinorelbine; Topotecan; Pemetrexed; Mitomycins; Mitomycin; Cetuximab; Dasatinib; Raltitrexed
• Other Study ID Numbers: CNIO-GI-01-2012