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Colorectal CancerPhase 2POSIBANCT01276379

Study Evaluating Biomarkers in Patients With Colorectal Cancer and Native KRAS Treated With Chemotherapy + Cetuximab

A Phase 2 study testing FOLFIRI (m), FOLFOX-6 (m) and Cetuximab in people with Colorectal Cancer, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 27 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Advanced colorectal cancer (ACRC) is a heterogeneous disease and classification of patients is nowadays inefficient. Roughly twenty per cent of patients present with favorable figures (less than 4 liver nodules and less than 5 cm) and are suitable for local treatments (surgery or local-ablative therapies). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
FOLFIRI (m), FOLFOX-6 (m) and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
221 participants
Where
27 sitesSpain
Study dates
Jan 2011to 21 Dec 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age ≥ 18 years
  • Able to sign an informed consent form
  • Advanced and/or metastatic colorectal cancer
  • Colorectal cancer with KRAS wild type genotype
  • At least one unidimensionally measurable lesion according to RECIST criteria (1.1 revised) (to be assessed ≤ 28 days prior to the study treatment)
  • All patients with the following features will be included:
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  • Progression free survival > 6 months after adjuvant treatment +/- radiotherapy
  • "De novo" diagnosis of the disease
  • Performance ECOG status of 0-2
  • Life expectancy ≥ 3 months
  • Adequate bone marrow function: neutrophils ≥1,5 x 10^9/L; platelets ≥ 100 x 10^9/L; hemoglobin ≥9 g/dL.
  • Adequate liver, renal and hematological function as follows:
  • Adequate liver function: SGOT and SGPT 2.5 x ULN (5 x ULN in case of hepatic metastasis). Total bilirubin < 1,5 x ULN. Alkaline phosphatase 2,5 x LSN (5 x ULN if hepatic metastasis or 10 x ULN if bone metastasis)
  • Creatinine clearance or creatinine clearance during 24 hours ≥ 50 mL/min
  • Magnesium ≥ LLN, calcium ≥ LLN

Who cannot join

  • PS > 2 or elderly patients with fragility criteria
  • Previous surgery for metastasis
  • Previous systemic treatment for the metastatic colorectal cancer
  • Previous treatment with antibodies anti-EGFR or treatment with small-molecule EGFR tyrosine kinase inhibitors or EGFR signal transduction inhibitors. Subjects who suspend their first dose due to a reaction to the infusion can participate
  • Central nervous system metastasis (except: treated subjects with asymptomatic CNS metastasis who have not received steroids within the 30 days prior to inclusion)
  • Prior malignant tumor in the last 5 years, except: basal cell carcinoma of the skin or pre-invasive cervical cancer
Show all 24Show fewer
  • Unresolved toxicities from a prior systemic treatment which do not qualify the patient for inclusion
  • Presence of peripheral neuropathy (degree > 1 in the ctc version 3.0) and serious nonhealing wound, ulcer, or bone fracture
  • Hormonal treatment, immunotherapy or experimental or approved antibodies/proteins ≤ 30 days before the inclusion
  • Uncontrolled serious cardiovascular disease or: congestive cardiac failure NYHA lll or lV, unstable angina pectoris, myocardial infarction precedents in the past 12 months, significant arrhythmias
  • Interstitial pneumonitis or pulmonary fibrosis precedents, or interstitial pneumonitis or pulmonary fibrosis signs on the thoracic CT-scan
  • Treatment for systemic infection within the 14 days prior to treatment
  • Acute/subacute intestinal occlusion and/or active inflammatory bowel disease or any other bowel disease producing chronic diarrhea
  • Precedent of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency
  • Precedent of any disease which can increase the risks associated to the participation in the study or interfere in the study results
  • Known positive test for the following infections: HIV, Hepatitis C + abnormal liver enzymes values, active chronic Hepatitis B (except Hepatitis C seropositive with normal liver enzymes)
  • All concurrent diseases which can increase the toxicity risk
  • The individual presents a disorder of any kind which jeopardizes their ability to give their written consent form and/or fulfill the study procedures
  • Any investigational agent within 30 days before enrolment
  • Pregnant or breastfeeding woman, or planning to get pregnant within the 6 months after treatment
  • Surgery (excluding the diagnostic biopsy or placing of a central venous catheter)
  • Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the study and 6 months after de last administration for women, and 1 month for men
  • Unability to fulfill the study requirements by the patients
  • Psychological, family, sociological or geographical conditions that may interfere with the fulfillment of the study protocol and the follow-up calendar

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

Spain27 sites

  • Complejo Hospitalario Universitario de Albacete

    Albacete

  • Hospital Infanta Cristina de Badajoz

    Badajoz

  • Hospital de Barbastro

    Barbastro

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital General Yagüe

    Burgos

  • Hospital San Pedro de Alcántara

    Cáceres

  • Hospital Sant Jaume de Calella

    Calella

  • Hospital Provincial de Castellón

    Castellon, Castellón

  • Hospital General Universitario de Elche

    Elche

  • Hospital de Jaén

    Jaén

  • Hospital Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida

  • Fundación Jimenez Díaz

    Madrid

  • Hospital de Móstoles

    Madrid

  • Hospital Universitario la Paz

    Madrid

  • Hospital de Mataró

    Mataró

  • Hospital Son Espases

    Palma, Malllorca

  • Hospital Son Llàtzer

    Palma, Mallorca

  • Clínica Universitaria de Navarra

    Pamplona

  • Hospital de Navarra

    Pamplona

  • Hospital Sant Joan de Reus

    Reus, Tarragona

  • Hospital de Sagunto

    Sagunto

  • Mutua de Terrassa

    Terrassa

  • Hospital Virgen de la Salud

    Toledo

  • Instituto Valenciano de Oncología

    Valencia

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

  • Hospital Miguel Servet

    Zaragoza

Other trials in Spain

About this study

Official title: Single-Arm, Multicenter, Prospective, Phase 2 Study for the Evaluation of Biomarkers in Patients With Advanced &/or Metastatic Colorectal Cancer With Wild Type KRAS Treated Biweekly With Chemotherapy and Cetuximab as First-Line Treatment

Advanced colorectal cancer (ACRC) is a heterogeneous disease and classification of patients is nowadays inefficient. Roughly twenty per cent of patients present with favorable figures (less than 4 liver nodules and less than 5 cm) and are suitable for local treatments (surgery or local-ablative therapies). Additionally, 10-15% of patients have poor performance status (PS >2) or are severe disabled due to geriatric syndromes or/and co-morbid diseases that preclude any treatment strategies than best supportive care alone. The rest of patients (fit patients not suitable for radical treatments) constitute the population of patients treated with palliative therapies. Despite of it not all these patients have the same prognosis. Patients with PS 0,1 and levels of LDH <ULN (Intermediate-risk patients) have better PFS and OS irrespective of therapy in all randomized clinical trials (de Gramont et al, JCO 2000; Douillard et al, Lancet 2000; Koopman et al, 2007).

CRYSTAL trial shows a benefit in PFS (1.5 months) in RASWT of FOLFIRI plus cetuximab compared with FOLFIRI alone. Nowadays the selection of patients for cetuximab treatment is based on mutational status of KRAS, which allow to select those patients who will not respond to therapy. Other surrogate markers of activity should be also evaluated. Our hypothesis is that the suggested biomarkers will allow the selection of the patients who will benefit the most from the biweekly cetuximab treatment.

Being tested
FOLFIRI (m), FOLFOX-6 (m), Cetuximab
Keywords
colorectal cancer, advanced, metastatic, KRAS, biomarkers (BRAF, IGF1P/MMp7,PI3K-PTEN), cetuximab
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFIRI (m)Drug

    Also called folinic acid, fluorouracil and irinotecan.

    FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be:

    • Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle.
    • l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1.
    • One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1.
    • 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours.

  • FOLFOX-6 (m)Drug

    Also called folinic acid, fluorouracil and oxaliplatin.

    FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be:

    • Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle.
    • l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1.
    • One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1.
    • 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours.

  • CetuximabDrug

    Also called erbitux

    • 500 mg/m2 i.v. Every 2 weeks.
Study groups in NCT01276379
Study groupRoleWhat they receive
FOLFIRI (m) or FOLFOX-6 (m) + cetuximabExperimentalFOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy.
Receives: Drug: FOLFIRI (m); Drug: FOLFOX-6 (m); Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival

    Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Two groups will be defined based on the score built from the proposed clinical variables and biomarkers. Instead of a binomial distribution, a Log-rank method has been used to calculate the sample size in order to include all the incidents during the follow-up. Expecting a minimum 20% difference (60 vs. 40%) on PFS at 12 months between groups and with the following assumptions:

    Alpha error (bilateral): 5% Beta error: 20% Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

    Measured: 4 years

Secondary outcomes (5)

  1. Overall Survival

    Measured as time in months from start of study treatment to death or lost to follow up.

    Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

    Measured: 4 years

  2. Response Duration

    Duration of the partial or total response to the treatment. Evaluation and classification according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors)

    Measured: 4 years

  3. Frequency of Adverse Events

    Frequency and type of adverse events (AEs). AEs were coded according to NCI CTCAE V3.0 and classified by frequency, relatedness to study treatment (related/not related) and severity (Grade).

    Severity ranges from grade 1 (low intensity) to Grade 5 (max. intensity, death)

    Measured: 4 years

  4. Secondary Biomarkers Analysis

    The secondary biomarkers in serum and tumoral tissue will be analysed in order to predict the acquired resistance.

    Measured: 4 years

  5. Tumoral Response

    Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2011 (estimated)
  2. Study startJan 2011
  3. Primary completion15 Mar 2017
  4. Study completion21 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Screening
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
221 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01276379
Sponsor's protocol ID
GEMCAD-1002
Other IDs
2010-019236-12
Acronym
POSIBA
Status last verified
Jun 2021
First submitted
12 Jan 2011
Last updated
2 Jul 2021
Data monitoring committee
Yes

Publications

  • Maurel J, Alonso V, Escudero P, Fernandez-Martos C, Salud A, Mendez M, Gallego J, Rodriguez JR, Martin-Richard M, Fernandez-Plana J, Manzano H, Mendez JC, Zanui M, Falco E, Gil-Raga M, Aparicio J, Feliu J, Garcia-Albeniz X, Torres F, Rojo F, Bellosillo B, Mendiola M, Fernandez V, Reig O, Claes B, Maertens G, Sablon E, Jacobs B, Montagut C. Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy. JCO Precis Oncol. 2019 Dec;3:1-16. doi: 10.1200/PO.18.00289.

    PubMed 35100697

  • Garcia-Albeniz X, Alonso V, Escudero P, Mendez M, Gallego J, Rodriguez JR, Salud A, Fernandez-Plana J, Manzano H, Zanui M, Falco E, Feliu J, Gil M, Fernandez-Martos C, Bohn U, Alonso C, Calderero V, Rojo F, Cuatrecasas M, Maurel J. Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02). Oncologist. 2019 Nov;24(11):e1115-e1122. doi: 10.1634/theoncologist.2018-0728. Epub 2019 Jun 24.

    PubMed 31235483

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FOLFIRI (m), FOLFOX-6 (m) and Cetuximab in people with Colorectal Cancer, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 27 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01276379, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2021.

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