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Trial record 1 of 1 for:    GEMCAD-16-03
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FOLFIRI + Panitumumab First-line Treatment in Elderly Patients With Unresectable Metastatic Colorectal Cancer, RAS/BRAF Wild-type and Good Performance Status (OPALO)

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ClinicalTrials.gov Identifier: NCT03142516
Recruitment Status : Active, not recruiting
First Posted : May 5, 2017
Last Update Posted : February 8, 2019
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 one year in elderly patients with RAS/BRAF wild-type unresectable mCRC and good performance status treated with FOLFIRI + panitumumab as first-line therapy.

The clinical hypothesis of this study is that the combination of panitumumab and FOLFIRI is a good treatment option in elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC. Another purpose of this clinical trial is to determine the RAS/BRAF mutation status in liquid biopsies at baseline and at the time of disease progression.


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

Detailed Description:

Phase II, multicentre, single-arm trial. Elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC will be evaluated before being included in this trial. Eligible patients will receive panitumumab plus FOLFIRI for disease control until disease progression, unacceptable toxicity, investigator decision or the patient's withdrawal of consent.

Tumour response will be evaluated by investigators using RECIST criteria (Response Evaluation Criteria in Solid Tumours) version 1.1. Tumour response will be evaluated every 8 weeks until disease progression is documented. Disease response will be confirmed no less than 28 days after the criteria for response are first met. Radiographic progression of subjects with symptoms indicating disease progression will be evaluated at the time of symptom onset.

Following disease progression, information will be collected on the subsequent lines of treatment chosen by the investigator and survival at follow-up visits held every 12 weeks (± 4 weeks) until completion of the trial (approximately 24 months after inclusion of the last patient in the trial).

A blood sample will be taken at baseline and at the time of disease progression in order to determine the RAS/BRAF mutation status.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial to Evaluate the Efficacy and Safety of FOLFIRI + Panitumumab as First-line Treatment in Elderly Patients With RAS/BRAF Wild-type Unresectable Metastatic Colorectal Cancer and Good Performance Status
Actual Study Start Date : October 31, 2017
Estimated Primary Completion Date : January 31, 2021
Estimated Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Panitumumab

Arm Intervention/treatment
Experimental: FOLFIRI + panitumumab

All patients will receive panitumumab plus FOLFIRI for disease control 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: 150 mg/m2 as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle.
  • 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 150 mg/m2 will be administered as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle
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:
  • Leucovorin
  • Any marketed

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:
  • 5-fluorouracil
  • Any marketed




Primary Outcome Measures :
  1. Progression-free survival at one year [ Time Frame: 12 months after inclusion ]
    Percentage of subjects still alive and progression free 12 months after inclusion in the study


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 42 months ]
    Time (months) from inclusion in the trial until disease progression or death

  2. Objective response rate [ Time Frame: 42 months ]
    Proportion of patients with an objective response (complete or partial response) according to RECIST 1.1 criteria

  3. Disease control rate [ Time Frame: 42 months ]
    Proportion of patients with disease control (complete response, partial response or stable disease)

  4. Duration of response [ Time Frame: 42 months ]
    Time (months) from the first confirmation of objective response according to RECIST 1.1 criteria until disease progression or death

  5. Time to response [ Time Frame: 18 months ]
    Time (months) from inclusion in the trial until the date of the first confirmation of objective response according to RECIST 1.1 criteria

  6. Overall survival (OS) [ Time Frame: 42 months ]
    Time (months) from inclusion in the trial until death of the patient

  7. Time to treatment failure [ Time Frame: 18 months ]
    Time (months) from inclusion in the trial until progression, death or discontinuation due to toxicity

  8. Proportion of patients with early tumour shrinkage (ETS) [ Time Frame: 2 months ]
    Defined as tumour shrinkage ≥ 30% at the first tumour assessment based on RECIST 1.1 criteria

  9. Depth of response (DpR) [ Time Frame: 18 months ]
    Measured as the maximum reduction ratio (percentage) of the tumour compared with baseline measurement (sum of diameters of the lesions) at the different assessments based on RECIST 1.1 criteria

  10. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 42 months ]
    Incidence and severity of adverse events. AEs description according to the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

  11. Combined analysis of prognostic factors in metastatic disease [ Time Frame: 42 months ]
    To analyse the number of lesions in liver and lung disease (1-3 vs 4-9 or ≥10), and the size of the largest lesion (<5 cm or ≥ 5 cm), in correlation with the analytical values, mainly LDH and AP values.


Other Outcome Measures:
  1. RAS/BRAF conversion proportion [ Time Frame: At treatment initiation and at the time of PD (42 months) ]
    Conversion rate of RAS/BRAF status at first-line treatment initiation and at the time of disease progression

  2. RAS/BRAF mutations' detection proportion [ Time Frame: At baseline ]
    Detection rate of RAS/BRAF mutations in liquid biopsies at baseline in subjects with RAS/BRAF wild-type mCRC according to the solid biopsy analysis



Information from the National Library of Medicine

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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females ≥ 70 years,
  2. Able to understand, sign and date an informed consent form approved by the IEC,
  3. Histologically confirmed colorectal carcinoma with metastatic disease,
  4. RAS/BRAF wild-type status in solid biopsy confirmed prior to inclusion of the study,
  5. No previous treatment for metastatic disease,
  6. Patients starting therapy with FOLFIRI + panitumumab with a treatment aim other than achieving potential resectability of the disease,
  7. Independence in activities of daily living (ADL) based on the Katz Index and in instrumental activities of daily living (IAL) based on the Lawton Index,
  8. Having no or only one comorbidity according to the Charlson Comorbidity Index. The following ones are not considered comorbidities as long as it is provided they are adequately controlled with medication: gastroduodenal ulcer, diabetes without target organs' damage, chronic respiratory disease and connective tissue disease.
  9. Presence of at least one unidimensional measurable lesion ≥ 10 mm according to RECIST criteria (version 1.1),
  10. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1,
  11. Adequate bone marrow function: neutrophils ≥ 1.5 x 10^9/l; platelets ≥ 100 x 10^9/l; haemoglobin ≥ 9 g/dl,
  12. Hepatic, renal and metabolic function as follows:

    1. Total bilirubin count ≤ 1.5 x ULN; ALT and AST < 5 x ULN;
    2. Renal function, calculated creatinine clearance or 24-hour creatinine clearance ≥ 50 ml/min;
    3. Magnesium > LLN

Exclusion Criteria:

  1. Diagnosed or suspected central nervous system (CNS) metastasis,
  2. Patients with initially resectable metastases at the time of diagnosis of metastatic disease.
  3. History or presence of another malignancy, with the exception of curatively treated in situ carcinoma of the cervix or non-melanoma skin cancer or any curatively treated solid tumour, with no active disease or administration of treatment within 5 years prior to inclusion in the study,
  4. Prior treatment with irinotecan,
  5. Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed,
  6. Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (eg, cetuximab), anti- vascular endothelial growth factor (VEGF) or treatment with small molecule EGFR inhibitors (eg, erlotinib),
  7. Unresolved toxicities from prior systemic treatment that, in the investigator's opinion, make the patient unsuitable for inclusion,
  8. Hormone therapy, immunotherapy with experimental or approved antibodies/proteins (e.g. bevacizumab) ≤ 30 days prior to inclusion,
  9. Evidence of previous acute hypersensitivity reaction of any grade to any of the components of the treatment,
  10. History of interstitial lung disease or pulmonary fibrosis or signs of interstitial lung disease or pulmonary fibrosis on baseline CT,
  11. Presence of geriatric syndromes, defined as dementia, repeated falls, fecal incontinence or urinary incontinence,
  12. Acute or subacute bowel obstruction and/or active bowel disease or another bowel disease causing chronic diarrhoea (defined as diarrhoea of grade ≥ 2 according to the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE version 4.03),
  13. Significant cardiovascular disease, including unstable angina pectoris or myocardial infarction within 12 months prior to inclusion in the study,
  14. History of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency,
  15. Positive test result for human immunodeficiency virus, hepatitis C virus, chronic active hepatitis B infection,
  16. Treatment for systemic infection within 14 days prior to the start of the study treatment,
  17. Clinically significant sensory peripheral neuropathy,
  18. Any concurrent disease that may increase the risk associated with study participation or may interfere with the interpretation of study results,
  19. Any investigational product within 30 days prior to inclusion,
  20. Surgery (not including diagnostic biopsy or the placement of a central line) and/or radiotherapy within 28 days prior to inclusion in the study,
  21. Males whose partner is of child-bearing age and who does not agree to use adequate contraceptive precautions, i.e. double-barrier methods (e.g. diaphragm plus condom) or abstinence for the duration of the study and for 1 month after the last administration of the study drug,
  22. Subjects who do not agree or are unable to meet the study requirements,
  23. Psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and the follow-up schedule. Such conditions should be discussed with the patient before enrolment in the clinical 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): NCT03142516


Locations
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Spain
ICO L´Hospitalet de Llobregat - Hospital Durán i Reynals
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
Hospital Sant Joan Despí-Moises Broggi
Sant Joan Despí, Barcelona, Spain, 08970
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, Spain, 28222
Hospital Universitario Rey Juan Carlos
Móstoles, Madrid, Spain, 28933
Hospital Clínic
Barcelona, Spain, 08036
Hospital General Universitario de Elda
Elda, Spain, 03600
Hospital Universitario Arnau de Vilanova
Lleida, Spain, 25198
Hospital Universitario la Paz
Madrid, Spain, 28046
Hospital General Universitario Morales Meseguer
Murcia, Spain, 30008
Hospital Universitario Son Espases
Palma, Spain, 07020
Hospital Parc Taulí
Sabadell, Spain, 08208
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain, 50009
Sponsors and Collaborators
Grupo Espanol Multidisciplinario del Cancer Digestivo
Amgen
Pivotal S.L.
Investigators
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Study Director: Jaime Feliu, MD Hospital Universitario La Paz

Additional Information:
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Responsible Party: Grupo Espanol Multidisciplinario del Cancer Digestivo
ClinicalTrials.gov Identifier: NCT03142516     History of Changes
Other Study ID Numbers: GEMCAD-16-03
2017-001639-38 ( EudraCT Number )
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
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
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Grupo Espanol Multidisciplinario del Cancer Digestivo:
Clinical Trial, Phase II
Elderly
Aged
Disease-Free Survival
Safety
Tolerability
Chemotherapy regimen
Monoclonal antibody
FOLFIRI
Panitumumab
RAS/BRAF Wild-type

Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
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