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Trial record 1 of 1 for:    GEMCAD 17-01
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Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal (BEYOND)

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ClinicalTrials.gov Identifier: NCT03751176
Recruitment Status : Recruiting
First Posted : November 22, 2018
Last Update Posted : November 22, 2018
Sponsor:
Collaborators:
Amgen
Pivotal S.L.
Information provided by (Responsible Party):
Grupo Espanol Multidisciplinario del Cancer Digestivo

Brief Summary:

To estimate progression-free-survival at 6 months in subjects treated in first-line with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before starting second line treatment will be screened for this trial and who have interrupted panitumumab for <3 months (panitumumab continuation). Control arm of subjects treated with FOLFIRI alone will be included.

The combinations of 5-fluorouracil (5-FU) with oxaliplatin (FOLFOX)are considered the backbone chemotherapy for mCRC. Clinical trials have shown the benefit of adding monoclonal antibodies to subjects without mutations in RAS, directed against the epidermal growth factor receptor (EGFR) (cetuximab and panitumumab) to conventional chemotherapy as first-line treatment of mCRC. This trial purposes to study the treatment beyond progression with panitumumab in subjects treated in first-line with an anti-EGFR monoclonal antibody, or rather,the re-introduction of the same targeted therapy after progression to first line.

The clinical hypothesis of this study is that the second-line regimen FOLFIRI + panitumumab, is sufficiently active (defined as a 6-months PFS higher than 30% [based on prior results with second-line FOLFIRI alone] and of at least 50%), justifying further study in this population.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Drug: Panitumumab Drug: Irinotecan Drug: Folinic acid Drug: 5-FU Phase 2

Detailed Description:

A phase II, multicentre, open-label, randomized two-arm study. Subjects treated in first-line with panitumumab and FOLFOX and with wild type RAS mCRC confirmed in liquid biopsies before starting second line treatment will be screened for this trial. Only subjects who have interrupted panitumumab for < 3 months (panitumumab continuation) will be included.

Eligible subjects will receive FOLFIRI + panitumumab until disease progression, onset of unacceptable drug toxicities, or subject/physician's request to discontinue. A control arm of subjects treated with FOLFIRI alone will be included. Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right). A blood sample will be obtained at baseline and at disease progression in order to determine the mutational status of RAS/BRAF and other biomarkers.

Tumour response assessment will be performed by the investigator according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1). Subjects will be evaluated for tumour response every 8 weeks until documentation of disease progression. Responding disease will be confirmed no less than 28 days after the criteria for response are first met. Subjects with symptoms suggestive of progressive disease should be evaluated for tumour progression at the time the symptoms occur. After second-line treatment discontinuation, information on subsequent lines of treatments at the physician discretion and survival will be collected in follow-up visits carried out every 12 weeks (± 4 weeks) until the end of the study (approximately 20 months after the inclusion of the last subject in the study).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial to Evaluate the Efficacy of Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal Cancer Who Have Received FOLFOX + Panitumumab in First-line
Actual Study Start Date : November 8, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Panitumumab

Arm Intervention/treatment
Experimental: FOLFIRI + panitumumab

Patients received panitumumab plus FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:

  • Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy
  • FOLFIRI:
  • Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1
  • Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1
  • 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
Drug: Panitumumab
Panitumumab 6 mg/kg will be administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy
Other Name: Vectibix

Drug: Irinotecan
Irinotecan 180 mg/m2 will be administered as IV infusion over 90 min on day 1
Other Name: Any marketed

Drug: Folinic acid
Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1
Other Names:
  • Any marketed
  • Leucovorin

Drug: 5-FU
5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
Other Names:
  • Any marketed
  • 5-fluorouracil

Active Comparator: FOLFIRI

Patients received FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses:

  • Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1
  • Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1
  • 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2IV continuous infusion over 46-48 hours on days 1 and 2
Drug: Irinotecan
Irinotecan 180 mg/m2 will be administered as IV infusion over 90 min on day 1
Other Name: Any marketed

Drug: Folinic acid
Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1
Other Names:
  • Any marketed
  • Leucovorin

Drug: 5-FU
5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2
Other Names:
  • Any marketed
  • 5-fluorouracil




Primary Outcome Measures :
  1. Progression-free survival at 6 months [ Time Frame: 6 months after inclusion ]
    The proportion of subjects progression free at 6 months


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 38 months ]
    Time from randomization to progression or death (Kaplan-Meier estimate)

  2. Overall response rate (ORR) [ Time Frame: 38 months ]
    Proportion of subjects with an objective response (complete or partial response) per RECIST 1.1 criteria

  3. Overall survival (OS) [ Time Frame: 38 months ]
    Time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cut-off date censored at their last contact date (Kaplan-Meier estimate)

  4. Safety and tolerability. ( assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters) [ Time Frame: 38 months ]
    Safety assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters. AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  5. Biomarkers analysis by liquid biopsies. [ Time Frame: 38 months ]
    Conversion rate of RAS/BRAF status according to liquid biopsy determinations at second-line treatment initiation and at the time of disease progression after second-line treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Man or woman at least 18 years old
  2. Capable of understand, sign and date an informed consent approved by an IEC
  3. Histologically confirmed adenocarcinoma of the colon or rectum in subjects with metastatic disease
  4. Having received a 1st line chemotherapy regimen for mCRC consisting of FOLFOX + panitumumab and having at least achieved stable disease ( i.e., CR, PR or SD)
  5. Wild-type RAS tumour status confirmed in liquid biopsies before starting second-line treatment
  6. At least one unidimensionally measurable lesion of at least 10 mm per RECIST criteria (version 1.1)
  7. Subjects not candidates for metastasectomy
  8. Tumour disease staging according to RECIST (version 1.1) by investigator up to 4 weeks prior to start of study treatment
  9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  10. Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL
  11. Hepatic, renal and metabolic function as follows:

    • Total bilirubin count ≤1.5 x upper limit of normal (ULN), ALT and AST <2.5 x ULN; or in case of liver metastasis ALT and AST <5 x ULN
    • Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥ 50 mL/min
    • Magnesium > lower limit of normal (LLN) -

Exclusion Criteria:

  1. Diagnosis of progressive disease more than 3 months after the last panitumumab administration
  2. First-line PFS of less than 3 months
  3. Subjects given less than 3 months (consecutive) of first-line panitumumab
  4. History of prior or concurrent central nervous system (CNS) metastases
  5. History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 5 years before inclusion
  6. Prior irinotecan therapy
  7. Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the subject unfit for inclusion
  8. Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤ 30 days before inclusion (excluding panitumumab)
  9. Any investigational agent within 30 days prior to inclusion
  10. Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
  11. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography
  12. Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03)
  13. Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
  14. History of Gilbert disease or known dihydropyrimidine deficiency syndrome
  15. Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
  16. Treatment for systemic infection within 14 days before the start of study treatment
  17. Clinically significant peripheral sensory neuropathy
  18. History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results
  19. Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
  20. Pregnant or breastfeeding woman
  21. Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g., diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men
  22. The subject is unwilling or unable to meet the requirements of the study
  23. Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule. These conditions should be discussed with the subject before inclusion in the trial. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03751176


Contacts
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Contact: Jorge Aparicio, MD +34 606 563 508 japariciou@seom.org
Contact: Anna Triginer +34 93 434 44 12 secretaria@gemcad.org

Locations
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Spain
ICO Girona Dr. Josep Trueta Recruiting
Gerona, Barcelona, Spain, 17007
Contact: Xavier Hernández, MD       xhernandez@iconcologia.net   
Hospital de Granollers Recruiting
Granollers, Barcelona, Spain, 08402
Contact: Rosa Gallego, MD       mrgallego@fhag.es   
Hospital Mutua de Terrassa Recruiting
Terrassa, Barcelona, Spain, 08221
Contact: Julén Fernández, MD       julenfernandez@mutuaterrassa.cat   
Hospital General Universitario de Elche Recruiting
Alicante, Elche, Spain, 03203
Contact: Javier Gallego, MD       j.gallegoplazas@gmail.com   
Hospital Universitario Fundación Alcorcón Recruiting
Alcorcón, Madrid, Spain, 28922
Contact: Juan Carlos Cámara       jccamara@fhalcorcon.es   
H. Universitari Sant Joan de Reus Recruiting
Reus, Tarragona, Spain, 43204
Contact: Féliz Muñoz, MD       felix.munoz@grupsagessa.com   
Hospital de La Ribera de Alzira Recruiting
Alzira, Valencia, Spain, 46600
Contact: Teresa Taberner, MD       mttb2@hotmail.com   
Hospital Universitario Vall d`Hebron Recruiting
Barcelona, Spain, 08035
Contact: Jaume Capdevila, MD       jacapdevila@vhebron.net   
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Joan Maurel, MD       JMAUREL@clinic.cat   
Hospital de la Santa Creu I Sant Pau Recruiting
Barcelona, Spain, 08041
Contact: Anna Virgili, MD       avirgili@santpau.cat   
Hospital Universtiario la Paz Recruiting
Madrid, Spain, 28046
Contact: Nuria Rodriguez, MD       nuria.rodriguez@salud.madrid.org   
CIOCC Sanchinarro Recruiting
Madrid, Spain, 28050
Contact: Rafaél Álvarez, MD       ralvarezgallego@hmhospitales.com   
Complejo Hospitalario de Navarra Recruiting
Navarro, Spain, 31008
Contact: Ruth Vera, MD       ruth.vera.garcia@cfnavarra.es   
Corporació Sanitaria Parc Taulí Recruiting
Sabadell, Spain, 08208
Contact: ismael Macías, Md       imacias@tauli.cat   
Fundación Instituto Valenciano de Oncología Not yet recruiting
Valencia, Spain, 46009
Contact: Carlos Fernandez-Martos, MD         
Hospital Universitario Dr. Peset Recruiting
Valencia, Spain, 46017
Contact: Carles Bosch, MD       bosch_car@gva.es   
Hospital Universitario y Politécnico La Fe Not yet recruiting
Valencia, Spain, 46026
Contact: Jorge Aparicio, MD       japariciou@seom.org   
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo
Amgen
Pivotal S.L.
Investigators
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Study Director: Jorge Aparicio, MD Hospital universitari i Politecnic La Fe

Additional Information:
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Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT03751176     History of Changes
Other Study ID Numbers: GEMCAD-17-01
2017-004519-38 ( EudraCT Number )
First Posted: November 22, 2018    Key Record Dates
Last Update Posted: November 22, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
Clinical trial, phase II
Aged (at least 18 years old)
Progression -Free - Survival
Safety
Conversion rate of RAS/BRAF status in liquid biopsy
Chemotherapy regimen
Monoclonal antibody
FOLFIRI
Panitumumab
RAS/BRAF Wild-type

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Panitumumab
Leucovorin
Levoleucovorin
Folic Acid
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological
Antidotes
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances