Study Assessing Potential Predictive Tumor Markers in Metastatic Colorectal Cancer (PULSE)

May 11, 2018 updated by: Grupo Espanol Multidisciplinario del Cancer Digestivo

An Open Label, Phase II Study Assessing Potential Predictive Tumor Markers in Patients With Metastatic Colorectal Cancer and Wild Type K-RAS Tumor Treated With FOLFOX Plus Panitumumab as First-line Therapy

To estimate the progression free survival for subjects treated with panitumumab in combination with a chemotherapy regimen of oxaliplatin, 5-Fluorouracil (5-FU) and leucovorin (FOLFOX) as first-line chemotherapy regimen for subjects with metastatic colorectal cancer with WT (wild type) KRAS according to the IGFRp (protein receptor insulin growth factor) and MMP-7 (Matrilysin) expression.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

By transactivation, phosphorylated insulin growth factor receptor I (p-IGF-IR) can activate epidermal growth factor receptor (EGFR). Matrilysin (MMP-7), can activate IGF-IR (insulin-like growth factor receptor ) by degrading IGFBP-3 (Insulin-like growth factor-binding protein 3) and releasing IGF-I (Insulin-like growth factor 1). Concomitant expression of MMP-7 and p-IGF-IR (using a specific monoclonal antibody (p-1316) recognizing the phosphorylated carboxy-terminal part of the IGF-IR) (DP (Double Positivity)) correlates with poor prognosis in WT KRAS patients treated with anti-EGFR antibodies plus irinotecan.The primary objective of this trial is to estimate the progression free survival (PFS) by DP (Double Positivity)immunohistochemistry (IHC) expression in patients with wild-type KRAS mCRC (metastatic colorectal cancer)treated with panitumumab and mFOLFOX6. Two groups are established by DP status (MMP7+/p-IGF-IR+ vs. MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR-). With a power of 80% and a bilateral alpha level of 0.05, assuming an accrual period of 12 months (m) and a follow-up period of 18 m, 40 patients are planned to be included in each group to detect a Hazard Ratio of 2. The median PFS of the DP group is expected to be 6 m and the total number of expected events is 56. Secondary objectives include disease control rate, duration of response, time to response and survival according the DP status. Neither interim analysis nor multiple comparison adjustment is planned.Treatment: Both groups will receive panitumumab 6 mg/kg and mFOLFOX6 every 2 weeks. If patients have not progressed after 6 m of treatment they will continue with panitumumab monotherapy until disease progression.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
      • Barcelona, Spain, 08041
        • Hospital de la Santa Creu i Sant Pau de Barcelona
      • Burgos, Spain, 09005
        • Complejo Asitencia de Burgos. Hospital General Yague
      • Ciudad Real, Spain, 13005
        • Hospital General de Ciudad Real
      • Girona, Spain, 17007
        • Institut Català d'Oncologia (ICO) de Girona
      • La Coruña, Spain, 15009
        • Centro Oncologico de Galicia
      • Las Palmas de Gran Canaria, Spain, 35010
        • Hosptial Dr. Negrin de Las Palmas de Gran Canaria
      • Lleida, Spain, 25198
        • Hospital Arnau de Vilanova de Lleida
      • Madrid, Spain, 28072
        • Hospital Infanta Sofía de Madrid
      • Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro de Madrid
      • Madrid, Spain, 28942
        • Hospital de Fuenlabrada de Madrid
      • Murcia, Spain, 30008
        • Hospital Morales Meseguer
      • Tarragona, Spain, 43003
        • Hosptial de Sant Pau i Santa Tecla de Tarragona
      • Valencia, Spain, 46009
        • Hospital La Fe de Valencia
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncología de Valencia
      • Valencia, Spain, 46014
        • Hospital General de Valencia
      • Valencia, Spain, 46017
        • Hospital Dr. Peset de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Miguel Servet de Zaragoza
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08906
        • Hosptial General de l'Hospitalet de Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Corporació Sanitaria Parc Taulí de Barcelona
      • Santa Coloma De Gramenet, Barcelona, Spain, 08923
        • Hospital de l'Esperit Sant
    • Castellon
      • Castellón De La Plana, Castellon, Spain, 12002
        • Consorcio Hospitalario Provincial de Castellon
    • Illes Balears
      • Palma De Mallorca, Illes Balears, Spain, 07010
        • Hospital Son Espases de Mallorca
      • Palma De Mallorca, Illes Balears, Spain, 07198
        • Hosptial Son Llatzer de Mallorca
    • La Rioja
      • Logroño, La Rioja, Spain, 26006
        • Hosptial de Logroño
    • Madrdi
      • Madrid, Madrdi, Spain, 28046
        • Hospital Universitario La Paz de Madrid
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universitaria de Navarra
      • Pamplona, Navarra, Spain, 31008
        • Hospital de Navarra
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36204
        • Hospital Xeral Cies de Vigo

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Man or woman ≥ 18 years.
  • Competent to comprehend, sign, and date an IEC-approved (Ethics Committee) informed consent form
  • Histologically-confirmed metastatic adenocarcinoma of the colon or rectum by the investigator.
  • Wild Type K-RAS colorectal cancer determined by the designated Central Laboratory prior to inclusion in the study in the primary tumor and/or at least one metastasis.
  • At least 1 uni-dimensionally measurable lesion of at least > 10 mm with spiral CT per modified RECIST criteria 1.1. (Response Evaluation Criteria In Solid Tumors)

  • Patients with the following characteristics will be included:

    1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval > than 6 months after its completion.
    2. Recurrence after adjuvant treatment with oxaliplatin +/- radiotherapy with a disease-free interval > than 12 months
    3. De novo diagnosis of the disease.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Life expectancy ≥ 3 months
  • Adequate bone marrow function
  • Adequate Hepatic and metabolic functions
  • Adequate Renal function
  • Magnesium > LLN (Lower limit of Normal)

Exclusion Criteria:

  • Patients they have received prior systemic therapy for the treatment of metastatic colorectal carcinoma.
  • Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, erlotinib) or EGFR signal transduction inhibitors.
  • Patients who had resection of metastatic disease
  • Central nervous system/brain metastases
  • Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer.
  • Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for inclusion
  • Presence of peripheral neuropathy (Common Toxicity Criteria (CTC) version 3.0 > grade 1), and of serious nonhealing wound, ulcer, or bone fracture.
  • Hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, bevacizumab) ≤ 30 days before inclusion
  • Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
  • History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan
  • Treatment for systemic infection within 14 days before initiating study treatment
  • Acute or sub-acute intestinal occlusion and /or active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day).
  • Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
  • Any investigational agent within 30 days before enrollment
  • Subject who is pregnant or breast feeding
  • Surgery (excluding diagnostic biopsy or central venous catheter placement) and/or radiotherapy within 14 days prior to inclusion in the study.
  • Woman or man of childbearing potential not consenting to use adequate contraceptive precautions

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Panitumumab + FOLFOX (DP)
Panitumumab and FOLFOX will be administered to patients with DP (MMP7+/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Drug: Panitumumab + FOLFOX (DP)
Panitumumab and FOLFOX will be administered to patients with DP once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Experimental: Panitumumab + FOLFOX (no-DP)
Panitumumab and FOLFOX will be administered to patients with no-DP (MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.
Drug: Panitumumab + FOLFOX (no-DP)
Panitumumab and FOLFOX will be administered to patients with no-DP (MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR) once every 14 days until 6 months of treatment or until disease progression (PD) or unacceptable toxicity. If patients have not progressed after 6 months of treatment with panitumumab and FOLFOX they will continue with panitumumab monotherapy until disease progression.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free survival time according to the MMP7 status (PFS)
Time Frame: 5 years
To estimate the PFS by DP immunohistochemistry (IHC) expression in patients with wild-type KRAS mCRC treated with panitumumab and mFOLFOX6. Two groups are established by DP status (MMP7+/p-IGF-IR+ vs. MMP7+/p-IGF-IR-, MMP7-/p-IGF-IR+ or MMP7-/p-IGF-IR-).
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of response (DOR)
Time Frame: 5 years
Time from first confirmed objective response to radiologic disease progression per modified RECIST criteria.
5 years
Time to response (TTR)
Time Frame: 5 years
Time from randomization date to date of first confirmed objective response
5 years
Time to treatment failure (TtTF)
Time Frame: 5 years
Time from enrolment to the date the decision was made to end the treatment phase for any reason.
5 years
Objective response rate (ORR)
Time Frame: 5 years
Incidence of either a confirmed CR or PR per modified RECIST criteria. CRs or PRs will be confirmed no less than 28 days after the criteria for response are first met. All subjects without a confirmed response will be considered non-responders.
5 years
Disease Control Rate (DCR)
Time Frame: 5 years
Incidence of either a confirmed CR or PR or stable disease (SD) while in the treatment phase; subjects prematurely discontinuing without a post baseline tumor response assessment or subjects with an observed response that is not confirmed will be considered non-responders otherwise.
5 years
Overall Survival (OS)
Time Frame: 5 years
Time from randomization date to date of death.
5 years
Time To Progression (TTP)
Time Frame: 5 years
Time from randomization date to date of radiologic disease progression per modified RECIST criteria.
5 years
Duration of Stable Disease (DoSD)
Time Frame: 5 years
Calculated for only those subjects with a best response of SD during the treatment period, time from enrolment to date of first observed PD or death due to PD (whichever comes first) in either the combination or monotherapy phases
5 years
Incidence and severity of AEs
Time Frame: 5 years
Incidence and severity of AEs (Common Toxicity Criteria version 3.0)
5 years
Molecular predictive markers for response.
Time Frame: 5 years
Molecular predictive markers for response.
5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Grupo Espanol Multidisciplinario del Cancer Digestivo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amgen
TFS Trial Form Support

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Joan Maurel, MD, Hospital Clinic i Provincial de Barcelona
  • Principal Investigator: Antonia Salud, MD, Hospital Arnau de Vilanova de Lleida
  • Principal Investigator: Antonio Arrivi, MD, Hospital Son Llatzer de Mallorca
  • Principal Investigator: Xavier Hernández, MD, Intitut Català d' Oncologia (ICO) de Girona
  • Principal Investigator: Ólbia Serra, MD, Hospital General de l'Hospitalet de Barcelona
  • Principal Investigator: Carles Pericay, MD, Corporació Sanitaria Parc Taulí de Barcelona
  • Principal Investigator: Isabel Busquier, MD, Consorcio Hospitalario Provincial de Castellon
  • Principal Investigator: Carlos Fernandez-Martos, MD, Instituto Valenciano de Oncología de Valencia
  • Principal Investigator: Jorge Aparicio, MD, Hospital Universitario La Fe de Valencia
  • Principal Investigator: Maria José Safont, MD, Hospital General Universitario de Valencia
  • Principal Investigator: Carles Bosch, MD, Hospital Dr. Peset de Valencia
  • Principal Investigator: Javier Gallego, MD, Hosptial General Universitario de Elche
  • Principal Investigator: Alberto Carmona, MD, Hosptial Morales Meseguer
  • Principal Investigator: Jaume Feliu, MD, Hosptial Universitario La Paz de Madrid
  • Principal Investigator: Ana Ruíz, MD, Hospital de Fuenlabrada de Madrid
  • Principal Investigator: Enrique Casado, MD, Hospital Infanta Sofía de Madrid
  • Principal Investigator: Ricardo Cubedo, MD, Hospital Universitario Puerta de Hierro de Madrid
  • Principal Investigator: Juana Maria Cano, MD, Hosptial General de Ciudad Real
  • Principal Investigator: Vicente Alonso, MD, Hospital Miguel Servet de Zaragoza
  • Principal Investigator: Monica Jorge, MD, Hospital Xeral Cies de Vigo
  • Principal Investigator: Herminio Manzano, MD, Hospital Son Dureta de Mallorca
  • Principal Investigator: Javier Rodríguez, MD, Clinica Universitaria de Navarra
  • Principal Investigator: Uriel Bohn, MD, Hosptial Dr. Negrin de Las Palmas de Gran Canaria
  • Principal Investigator: Miriam Zorrilla, MD, Hospital de Logroño
  • Principal Investigator: Carlos García, MD, Complejo Asistencial de Burgos. Hospital General Yague
  • Principal Investigator: Santiago Albiol, MD, Hospital de l'Esperit Sant de Barcelona
  • Principal Investigator: José Carlos Méndez, MD, Centro Oncológico de Galicia (La Coruña)
  • Principal Investigator: Francisco Javier Ramos, MD, Hospital de Sant Pau i Santa Tecla de Tarragona

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.

General Publications

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 8, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 13, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 13, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 24, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 1, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GEMCAD-0903
  • 2009-017331-18 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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