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Metastatic Colorectal CancerPhase 2PULSENCT01288339

Study Assessing Potential Predictive Tumor Markers in Metastatic Colorectal Cancer

A Phase 2 study testing Panitumumab + FOLFOX (DP) and Panitumumab + FOLFOX (no-DP) in people with Metastatic Colorectal Cancer, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 30 sites in Spain.

Completed

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

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Panitumumab + FOLFOX (DP) and Panitumumab + FOLFOX (no-DP)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
30 sitesSpain
Study dates
8 Nov 2010to 13 Feb 2015
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 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:
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  • Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval > than 6 months after its completion.
  • Recurrence after adjuvant treatment with oxaliplatin +/- radiotherapy with a disease-free interval > than 12 months
  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

Spain30 sites

  • Centro Oncológico de Galícia

    A Coruña, 15009

  • Hospital Clínic i Provincial de Barcelona

    Barcelona, 08036

  • Hospital de la Santa Creu i Sant Pau de Barcelona

    Barcelona, 08041

  • Complejo Asitencia de Burgos. Hospital General Yague

    Burgos, 09005

  • Consorcio Hospitalario Provincial de Castellon

    Castellon, Castellon, 12002

  • Hospital General de Ciudad Real

    Ciudad Real, 13005

  • Hospital General Universitario de Elche

    Elche, Alicante, 03203

  • Institut Català d'Oncologia (ICO) de Girona

    Girona, 17007

  • Hosptial General de l'Hospitalet de Barcelona

    L'Hospitalet de Llobregat, Barcelona, 08906

  • Hosptial Dr. Negrin de Las Palmas de Gran Canaria

    Las Palmas de Gran Canaria, 35010

  • Hospital Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hosptial de Logroño

    Logroño, La Rioja, 26006

  • Hospital Universitario La Paz de Madrid

    Madrid, Madrdi, 28046

  • Hospital Infanta Sofía de Madrid

    Madrid, 28072

  • Hospital Universitario Puerta de Hierro de Madrid

    Madrid, 28222

  • Hospital de Fuenlabrada de Madrid

    Madrid, 28942

  • Hospital Morales Meseguer

    Murcia, 30008

  • Hospital Son Espases de Mallorca

    Palma de Mallorca, Balearic Islands, 07010

  • Hosptial Son Llatzer de Mallorca

    Palma de Mallorca, Balearic Islands, 07198

  • Clínica Universitaria de Navarra

    Pamplona, Navarre, 31008

  • Hospital de Navarra

    Pamplona, Navarre, 31008

  • Corporació Sanitaria Parc Taulí de Barcelona

    Sabadell, Barcelona, 08208

  • Hospital de l'Esperit Sant

    Santa Coloma de Gramenet, Barcelona, 08923

  • Hosptial de Sant Pau i Santa Tecla de Tarragona

    Tarragona, 43003

  • Hospital La Fe de Valencia

    Valencia, 46009

  • Instituto Valenciano de Oncología de Valencia

    Valencia, 46009

  • Hospital General de Valencia

    Valencia, 46014

  • Hospital Dr. Peset de Valencia

    Valencia, 46017

  • Hospital Xeral Cies de Vigo

    Vigo, Pontevedra, 36204

  • Hospital Miguel Servet de Zaragoza

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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.

Read the 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.

Being tested
Panitumumab + FOLFOX (DP), Panitumumab + FOLFOX (no-DP)
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Panitumumab + FOLFOX (DP)Drug

    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.

  • Panitumumab + FOLFOX (no-DP)Drug

    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.

Study groups in NCT01288339
Study groupRoleWhat they receive
Panitumumab + FOLFOX (DP)ExperimentalPanitumumab 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.
Receives: Drug: Panitumumab + FOLFOX (DP)
Panitumumab + FOLFOX (no-DP)ExperimentalPanitumumab 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.
Receives: Drug: Panitumumab + FOLFOX (no-DP)

What is being measured

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

  1. Progression-free survival time according to the MMP7 status (PFS)

    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-).

    Measured: 5 years

Secondary outcomes (10)

  1. Duration of response (DOR)

    Time from first confirmed objective response to radiologic disease progression per modified RECIST criteria.

    Measured: 5 years

  2. Time to response (TTR)

    Time from randomization date to date of first confirmed objective response

    Measured: 5 years

  3. Time to treatment failure (TtTF)

    Time from enrolment to the date the decision was made to end the treatment phase for any reason.

    Measured: 5 years

  4. Objective response rate (ORR)

    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.

    Measured: 5 years

  5. Disease Control Rate (DCR)

    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.

    Measured: 5 years

  6. Overall Survival (OS)

    Time from randomization date to date of death.

    Measured: 5 years

  7. Time To Progression (TTP)

    Time from randomization date to date of radiologic disease progression per modified RECIST criteria.

    Measured: 5 years

  8. Duration of Stable Disease (DoSD)

    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

    Measured: 5 years

  9. Incidence and severity of AEs

    Incidence and severity of AEs (Common Toxicity Criteria version 3.0)

    Measured: 5 years

  10. Molecular predictive markers for response.

    Molecular predictive markers for response.

    Measured: 5 years

Timeline

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

  1. First posted2 Feb 2011 (estimated)
  2. Study start8 Nov 2010
  3. Primary completion13 Feb 2015
  4. Study completion13 Feb 2015

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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01288339
Sponsor's protocol ID
GEMCAD-0903
Other IDs
2009-017331-18, 2009
Acronym
PULSE
Status last verified
May 2018
First submitted
24 Dec 2010
Last updated
16 May 2018
Results posted
No
Data monitoring committee
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panitumumab + FOLFOX (DP) and Panitumumab + FOLFOX (no-DP) in people with Metastatic Colorectal Cancer, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 30 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 17 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 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 according to the MMP7 status (PFS) (time frame: 5 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 NCT01288339, which also lists 1 linked publication.

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 16 May 2018.

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