Colorectal NeoplasmsPhase 2OPALONCT03142516
FOLFIRI + Panitumumab First-line Treatment in Elderly Patients With Unresectable Metastatic Colorectal Cancer, RAS/BRAF Wild-type and Good Performance Status
A Phase 2 study testing Panitumumab, Irinotecan and Folinic acid in people with Colorectal Neoplasms and Colorectal Carcinoma, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 12 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Colorectal Neoplasms, Colorectal Carcinoma, Colorectal Cancer Metastatic
- What is being tested?
- Panitumumab, Irinotecan and Folinic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 12 sitesSpain
- Study dates
- 31 Oct 2017to 21 Jan 2021
- 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 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Males or females ≥ 70 years,
- Able to understand, sign and date an informed consent form approved by the IEC,
- Histologically confirmed colorectal carcinoma with metastatic disease,
- RAS/BRAF wild-type status in solid biopsy confirmed prior to inclusion of the study,
- No previous treatment for metastatic disease,
- Patients starting therapy with FOLFIRI + panitumumab with a treatment aim other than achieving potential resectability of the disease,
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- 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,
- 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.
- Presence of at least one unidimensional measurable lesion ≥ 10 mm according to RECIST criteria (version 1.1),
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-1,
- Adequate bone marrow function: neutrophils ≥ 1.5 x 10^9/l; platelets ≥ 100 x 10^9/l; haemoglobin ≥ 9 g/dl,
- Hepatic, renal and metabolic function as follows:
- Total bilirubin count ≤ 1.5 x ULN; ALT and AST < 5 x ULN;
- Renal function, calculated creatinine clearance or 24-hour creatinine clearance ≥ 50 ml/min;
- Magnesium > LLN
Who cannot join
- Diagnosed or suspected central nervous system (CNS) metastasis,
- Patients with initially resectable metastases at the time of diagnosis of metastatic disease.
- 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,
- Prior treatment with irinotecan,
- Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed,
- 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),
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- Unresolved toxicities from prior systemic treatment that, in the investigator's opinion, make the patient unsuitable for inclusion,
- Hormone therapy, immunotherapy with experimental or approved antibodies/proteins (e.g. bevacizumab) ≤ 30 days prior to inclusion,
- Evidence of previous acute hypersensitivity reaction of any grade to any of the components of the treatment,
- History of interstitial lung disease or pulmonary fibrosis or signs of interstitial lung disease or pulmonary fibrosis on baseline CT,
- Presence of geriatric syndromes, defined as dementia, repeated falls, fecal incontinence or urinary incontinence,
- 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),
- Significant cardiovascular disease, including unstable angina pectoris or myocardial infarction within 12 months prior to inclusion in the study,
- History of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency,
- Positive test result for human immunodeficiency virus, hepatitis C virus, chronic active hepatitis B infection,
- Treatment for systemic infection within 14 days prior to the start of the study treatment,
- Clinically significant sensory peripheral neuropathy,
- Any concurrent disease that may increase the risk associated with study participation or may interfere with the interpretation of study results,
- Any investigational product within 30 days prior to inclusion,
- Surgery (not including diagnostic biopsy or the placement of a central line) and/or radiotherapy within 28 days prior to inclusion in the study,
- 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,
- Subjects who do not agree or are unable to meet the study requirements,
- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Spain12 sites
Hospital Clínic
Barcelona, 08036
Hospital General Universitario de Elda
Elda, 03600
ICO L´Hospitalet de Llobregat - Hospital Durán i Reynals
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Arnau de Vilanova
Lleida, 25198
Hospital Universitario la Paz
Madrid, 28046
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Rey Juan Carlos
Móstoles, Madrid, 28933
Hospital General Universitario Morales Meseguer
Murcia, 30008
Hospital Universitario Son Espases
Palma, 07020
Hospital Parc Taulí
Sabadell, 08208
Hospital Sant Joan Despí-Moises Broggi
Sant Joan Despí, Barcelona, 08970
Hospital Clínico Universitario Lozano Blesa
Zaragoza, 50009
About this study
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
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.
Read the 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
- Being tested
- Panitumumab, Irinotecan, Folinic acid, 5-FU
- Keywords
- Clinical Trial, Phase II, Elderly, Aged, Disease-Free Survival, Safety, Tolerability, Chemotherapy regimen, Monoclonal antibody, FOLFIRI, Panitumumab, RAS/BRAF Wild-type
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
Also called Vectibix
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
IrinotecanDrug
Also called Any marketed
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 acidDrug
Also called Leucovorin, Any marketed
Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1
5-FUDrug
Also called 5-fluorouracil, Any marketed
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
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRI + panitumumab | Experimental | 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 Receives: Drug: Panitumumab; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival at one year
Percentage of subjects still alive and progression free 12 months after inclusion in the study
Measured: 12 months after inclusion
Secondary outcomes (11)
Progression-free survival (PFS)
Time (months) from inclusion in the trial until disease progression or death
Measured: 42 months
Objective response rate
Proportion of patients with an objective response (complete or partial response) according to RECIST 1.1 criteria
Measured: 42 months
Disease control rate
Proportion of patients with disease control (complete response, partial response or stable disease)
Measured: 42 months
Duration of response
Time (months) from the first confirmation of objective response according to RECIST 1.1 criteria until disease progression or death
Measured: 42 months
Time to response
Time (months) from inclusion in the trial until the date of the first confirmation of objective response according to RECIST 1.1 criteria
Measured: 18 months
Overall survival (OS)
Time (months) from inclusion in the trial until death of the patient
Measured: 42 months
Time to treatment failure
Time (months) from inclusion in the trial until progression, death or discontinuation due to toxicity
Measured: 18 months
Proportion of patients with early tumour shrinkage (ETS)
Defined as tumour shrinkage ≥ 30% at the first tumour assessment based on RECIST 1.1 criteria
Measured: 2 months
Depth of response (DpR)
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
Measured: 18 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
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
Measured: 42 months
Combined analysis of prognostic factors in metastatic disease
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.
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2017
- Study start31 Oct 2017
- Primary completion21 Jan 2021
- Study completion21 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol Multidisciplinario del Cancer Digestivo
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Pivotal S.L.
- Responsible party
- Sponsor
- Investigators
- Jaime Feliu, MD, Study director, Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142516
- Sponsor's protocol ID
- GEMCAD-16-03
- Other IDs
- 2017-001639-38, 2017
- Acronym
- OPALO
- Status last verified
- Jun 2021
- First submitted
- 2 May 2017
- Last updated
- 21 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03142516
- Acronym / sponsor ID
- OPALO / GEMCAD-16-03
- Conditions
- Colorectal Neoplasms, Colorectal Carcinoma, Colorectal Cancer Metastatic, Neoplasm Metastasis
- Keywords
- Clinical Trial, Phase II, Elderly, Aged, Disease-Free Survival, Safety, Tolerability, Chemotherapy regimen, Monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Grupo Espanol Multidisciplinario del Cancer DigestivoUniversity, hospital or other
- Collaborators
- Amgen, Pivotal S.L.
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 21 Jan 2021 (actual)
- Study completion
- 21 Jan 2021 (actual)
- First posted
- 5 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFIRI + panitumumab | Experimental | Drug: Panitumumab, Drug: Irinotecan, Drug: Folinic acid, Drug: 5-FUAll 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 |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (15 listed)
- Males or females ≥ 70 years,
- Able to understand, sign and date an informed consent form approved by the IEC,
- Histologically confirmed colorectal carcinoma with metastatic disease,
- RAS/BRAF wild-type status in solid biopsy confirmed prior to inclusion of the study,
- No previous treatment for metastatic disease,
Key exclusion criteria (23 listed)
- Diagnosed or suspected central nervous system (CNS) metastasis,
- Patients with initially resectable metastases at the time of diagnosis of metastatic disease.
- 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,
- Prior treatment with irinotecan,
- Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanitumumabAlso: VectibixPanitumumab 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 | Drug | FOLFIRI + panitumumab |
| IrinotecanAlso: Any marketedIrinotecan 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 | Drug | FOLFIRI + panitumumab |
| Folinic acidAlso: Leucovorin, Any marketedFolinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1 | Drug | FOLFIRI + panitumumab |
| 5-FUAlso: 5-fluorouracil, Any marketed5-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 | Drug | FOLFIRI + panitumumab |
Primary outcome
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
11 secondary outcomes
Progression-free survival (PFS)
Time frame: 42 months
Objective response rate
Time frame: 42 months
Disease control rate
Time frame: 42 months
Duration of response
Time frame: 42 months
Time to response
Time frame: 18 months
Overall survival (OS)
Time frame: 42 months
Time to treatment failure
Time frame: 18 months
Proportion of patients with early tumour shrinkage (ETS)
Time frame: 2 months
Depth of response (DpR)
Time frame: 18 months
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 42 months
Combined analysis of prognostic factors in metastatic disease
Time frame: 42 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
- GEMCAD web pageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaime Feliu, MD study director
Hospital Universitario La Paz
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panitumumab, Irinotecan and Folinic acid in people with Colorectal Neoplasms and Colorectal Carcinoma, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 12 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 23 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 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 at one year (time frame: 12 months after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jun 2021.