Treatment Related CancerPhase 2NCT04034173
Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation
A Phase 2 study testing Panitumumab, Irinotecan and Folinic acid in people with Treatment Related Cancer, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment Related Cancer
- 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
- 3 participants
- Where
- 1 siteGermany
- Study dates
- 24 Jul 2019to 22 Jun 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed, UICC stage IV metastatic adenocarcinoma of the colon or rectum
- Primarily non-resectable metastases or surgical resection refused by the patient
- RAS mutation determined by the local pathology
- Age ≥18
- ECOG performance status 0-2
- Patients suitable for chemotherapy administration
Show all 20Show fewer
- Patient's written declaration of consent obtained
- Estimated life expectancy > 3 months
- Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria
- Primary tumor tissue available and patient consents to storage and molecular and genetic profiling of tumor material. Molecular profiling of blood samples is optionally performed.
- Adequate bone marrow function:
- Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L
- Thrombocytes ≥ 100 x 109/L
- Haemoglobin ≥ 5.6 mmol/L (equivalent to 9 g/dL)
- Adequate hepatic function:
- Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
- ALAT and ASAT ≤ 2.5 x ULN (in the presence of hepatic metastases, ALAT and ASAT ≤ 5 x ULN)
- Adequate renal function:
- ▫ Creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50 mL/min
- No previous chemotherapy for metastatic disease. Patient with need of immediate treatment (high tumor load, symptoms) may have received one application of FOLFIRI prior to study treatment.
Who cannot join
- Previous chemotherapy for metastatic disease with the exception of one cycle of FOLFIRI (e.g. while waiting for the result of RAS mutation frequency).
- Patients planned to be treated with FOLFOX or another oxaliplatin-based regimen as first-line treatment
- Primarily resectable metastases and the patient agrees to resection
- Grade III or IV heart failure (NYHA classification)
- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
- Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
Show all 26Show fewer
- Participation in an investigational clinical study or experimental drug treatment within 30 days prior to study inclusion or within a period of 5 half-lives of the substances administered in the investigational clinical study or during an experimental drug treatment prior to inclusion in the study, depending on which period is longest
- Known hypersensitivity or allergic reaction to any of the following substances: 5-fluorouracil, folinic acid, panitumumab, irinotecan, and chemically related substances and/or hypersensitivity to any of the excipients of any of the aforementioned substances including known hypersensitivity reactions to monoclonal antibodies NCI CTCAE Grade ≥ 3.
- Known hypersensitivity to Chinese hamster ovary cell (CHO) - cellular products or other recombinant human or humanised monoclonal antibodies
- History of uncontrolled bronchial asthma
- Patients with interstitial pneumonitis or pulmonary fibrosis
- Patients with known brain metastasis
- History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
- Symptomatic peritoneal carcinomatosis
- Severe, non-healing wounds, ulcers or bone fractures
- Patients with acute or chronic infection requiring systemic therapy
- Known history of positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Active or chronic Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive; serologic tests required in patients who receive study treatment).
- Known DPD deficiency (specific screening not required)
- Known glucuronidation deficiency (Gilbert's syndrome);(specific screening not required
- Treatment with sorivudine or brivudine within 28 days before study enrollment or requirement for concomitant antiviral treatment with sorivudine or brivudine
- History of a second primary malignancy during the past 5 years before inclusion in the study or during participation in the study, with the exception of a basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, if these were treated curatively.
- Known previous or ongoing alcohol or drug abuse
- Pregnant or breast-feeding patients
- Any other severe concomitant disease or disorder which, in the investigator's opinion, could influence the patient's ability to participate in the study or influence his/her safety during the study or interfere with interpretation of study results
- Both, absent and restricted legal capacity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: FIRE-5 -Study: Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation
The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster development of resistance when sensitive cells are eradicated and when the RAS-mutant anti-EGFR resistant clones become predominant.
The characteristics of low-level RAS mutant tumors would be:
- Objective response rate (ORR) high (reflecting the sensitive clone)
- Progression-free survival (PFS) short (reflecting the more rapid outgrowth of RAS mutant clones)
- Conditions
- Treatment Related Cancer
- Being tested
- Panitumumab, Irinotecan, Folinic acid, 5-FU
- Keywords
- colorectal cancer, FIRE, low-RAS, mCRC, Panitumumab
- Medical subject headings
- Neoplasms, Second Primary, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanitumumabDrug
Panitumumab 6 mg/kg BW as 60-min i.v. infusion* D1
*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.
IrinotecanDrug
Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
Folinic acidDrug
Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
5-FUDrug
5-FU 400 mg/m² BSA, bolus, D1 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2
| Study group | Role | What they receive |
|---|---|---|
| RAS mutations frequency <= 7% | Other | Panitumumab 6 mg/kg BW as 60-min i.v. infusion* D1
*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.
Followed by FOLFIRI regimen
* Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
* Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
* 5-FU 400 mg/m² BSA, bolus, D1
* 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2
q day 14 Receives: Drug: Panitumumab; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-FU |
| RAS mutation frequency >7% to <=14% | Other | Panitumumab 6 mg/kg BW as 60-min i.v. infusion* D1
*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.
Followed by FOLFIRI regimen
* Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
* Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
* 5-FU 400 mg/m² BSA, bolus, D1
* 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2
q day 14 Receives: Drug: Panitumumab; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-FU |
| RAS mutation frequency >14% to <=20% | Other | Panitumumab 6 mg/kg BW as 60-min i.v. infusion* D1
*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.
Followed by FOLFIRI regimen
* Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
* Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
* 5-FU 400 mg/m² BSA, bolus, D1
* 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2
q day 14 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.
Overall Response Rate
As primary endpoint ORR according to RECIST 1.1 will be evaluated separately for each arm of patients with defined low-frequency RAS mutation
Measured: up to 60 months
Secondary outcomes (4)
Progression free survival (PFS)
PFS, separately for each arm of patients with defined low-frequency RAS mutation
Measured: up to 60 months
Overall Survival (OS)
OS, separately for each arm of patients with defined low-frequency RAS mutation
Measured: up to 60 months
Investigation of Early Tumor shrinkage (ETS) as an alternative early-on-treatment predictor of treatment efficacy
ETS, separately for each group of patients with defined low-frequency RAS mutation
Measured: up to 48 months
Investigation of Depth of Response (DpR) to define the nadir of tumour response
DpR, separately for each arm of patients with defined low-frequency RAS Mutation.
Measured: up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2019
- Study start24 Jul 2019
- Primary completion22 Jun 2021
- Study completion22 Jun 2021
Why it stopped: Funding was withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Related CancerStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, ClinAssess GmbH
- Responsible party
- Principal investigator, PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich
- Investigators
- Dominik Modest, PD Dr., Study chair, Ludwigs Maximilians University Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04034173
- Sponsor's protocol ID
- FIRE-5
- Status last verified
- Aug 2026
- First submitted
- 22 Jan 2019
- Last updated
- 27 Aug 2026
- 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 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FIRE-5 -Study: Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation
- ClinicalTrials.gov ID
- NCT04034173
- Acronym / sponsor ID
- FIRE-5
- Conditions
- Treatment Related Cancer
- Keywords
- colorectal cancer, FIRE, low-RAS, mCRC, Panitumumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding was withdrawn
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Collaborators
- Amgen, ClinAssess GmbH
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 22 Jun 2021 (actual)
- Study completion
- 22 Jun 2021 (actual)
- First posted
- 26 Jul 2019 (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.
The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster development of resistance when sensitive cells are eradicated and when the RAS-mutant anti-EGFR resistant clones become predominant.
The characteristics of low-level RAS mutant tumors would be:
- Objective response rate (ORR) high (reflecting the sensitive clone)
- Progression-free survival (PFS) short (reflecting the more rapid outgrowth of RAS mutant clones)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| RAS mutations frequency <= 7% | Other | Drug: Panitumumab, Drug: Irinotecan, Drug: Folinic acid, Drug: 5-FUPanitumumab 6 mg/kg BW as 60-min i.v. infusion* D1 *If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14 |
| RAS mutation frequency >7% to <=14% | Other | Drug: Panitumumab, Drug: Irinotecan, Drug: Folinic acid, Drug: 5-FUPanitumumab 6 mg/kg BW as 60-min i.v. infusion* D1 *If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14 |
| RAS mutation frequency >14% to <=20% | Other | Drug: Panitumumab, Drug: Irinotecan, Drug: Folinic acid, Drug: 5-FUPanitumumab 6 mg/kg BW as 60-min i.v. infusion* D1 *If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed, UICC stage IV metastatic adenocarcinoma of the colon or rectum
- Primarily non-resectable metastases or surgical resection refused by the patient
- RAS mutation determined by the local pathology
- Age ≥18
- ECOG performance status 0-2
Key exclusion criteria (26 listed)
- Previous chemotherapy for metastatic disease with the exception of one cycle of FOLFIRI (e.g. while waiting for the result of RAS mutation frequency).
- Patients planned to be treated with FOLFOX or another oxaliplatin-based regimen as first-line treatment
- Primarily resectable metastases and the patient agrees to resection
- Grade III or IV heart failure (NYHA classification)
- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
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 |
|---|---|---|
| PanitumumabPanitumumab 6 mg/kg BW as 60-min i.v. infusion* D1 *If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. | Drug | RAS mutation frequency >14% to <=20%, RAS mutation frequency >7% to <=14%, RAS mutations frequency <= 7% |
| IrinotecanIrinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 | Drug | RAS mutation frequency >14% to <=20%, RAS mutation frequency >7% to <=14%, RAS mutations frequency <= 7% |
| Folinic acidFolinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 | Drug | RAS mutation frequency >14% to <=20%, RAS mutation frequency >7% to <=14%, RAS mutations frequency <= 7% |
| 5-FU5-FU 400 mg/m² BSA, bolus, D1 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 | Drug | RAS mutation frequency >14% to <=20%, RAS mutation frequency >7% to <=14%, RAS mutations frequency <= 7% |
Primary outcome
Overall Response Rate
Time frame: up to 60 months
As primary endpoint ORR according to RECIST 1.1 will be evaluated separately for each arm of patients with defined low-frequency RAS mutation
4 secondary outcomes
Progression free survival (PFS)
Time frame: up to 60 months
Overall Survival (OS)
Time frame: up to 60 months
Investigation of Early Tumor shrinkage (ETS) as an alternative early-on-treatment predictor of treatment efficacy
Time frame: up to 48 months
Investigation of Depth of Response (DpR) to define the nadir of tumour response
Time frame: up to 48 months
Results and safety
The study was stopped early (reason given: Funding was withdrawn). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Treatment Related Cancer
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 3
Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas
Metastatic Dedifferentiated Liposarcoma, Metastatic Undifferentiated Pleomorphic Sarcoma
Active, not recruiting
Predictive Markers of Immune-related Adverse Events in Patients Treated With Immune Stimulatory Drugs
Cancer
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Enrolling by invitation
Dance-Based Exercise for Cancer-Related Fatigue in Breast Cancer Patients
Breast Neoplasms
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.
Dominik Modest, PD Dr. study chair
Ludwigs Maximilians University Munich
1 site 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 Treatment Related Cancer, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
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 20 inclusion and 26 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: stopped early, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 was stopped early (reason given: Funding was withdrawn). Results are not available in the source record.
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?
Overall Response Rate (time frame: up to 60 months). 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 27 Aug 2026.