FOLFIRI + Panitumumab First-line Treatment in Elderly Patients With Unresectable Metastatic Colorectal Cancer, RAS/BRAF Wild-type and Good Performance Status

NCT ID: NCT03142516

Last Updated: 2021-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-31
• Study Completion Date: 2021-01-21

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.

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.

Conditions

Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Cancer Metastatic; Neoplasm Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: DRUG

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

Irinotecan

Intervention Type: DRUG

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

Folinic acid

Intervention Type: DRUG

Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1

5-FU

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Folinic acid

Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Vectibix; Any marketed; Leucovorin; Any marketed; 5-fluorouracil; Any marketed

Eligibility 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

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Pivotal S.L.

INDUSTRY

Sponsor Role: collaborator

Grupo Espanol Multidisciplinario del Cancer Digestivo

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaime Feliu, MD

Role: STUDY_DIRECTOR

Hospital Universitario La Paz

Locations

ICO L´Hospitalet de Llobregat - Hospital Durán i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Sant Joan Despí-Moises Broggi

Sant Joan Despí, Barcelona, Spain

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, Spain

Hospital Clínic

Barcelona, , Spain

Hospital General Universitario de Elda

Elda, , Spain

Hospital Universitario Arnau de Vilanova

Lleida, , Spain

Hospital Universitario la Paz

Madrid, , Spain

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Hospital Universitario Son Espases

Palma, , Spain

Hospital Parc Taulí

Sabadell, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Countries

Spain

Related Links

https://www.gemcad.es/

GEMCAD web page

Other Identifiers

2017-001639-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEMCAD-16-03

Identifier Type: -

Identifier Source: org_study_id