Metastatic Colorectal CancerPhase 2FOCULMNCT02063529
FOLFOXIRI With or Without Cetuximab as First-line Treatment of Patients With Non-resectable Liver - Only Metastatic Colorectal Cancer
A Phase 2 study testing FOLFOXIRI + Cetuximab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
PURPOSE: A primary aim of phase II FOCULM study is to explore whether cetuximab in combination with FOLFOXIRI as first treatment could improve surgical conversion in patients with KRAS/NRAS wild-type, unresectable liver - only metastases of colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- FOLFOXIRI + Cetuximab and FOLFOXIRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 1 siteChina
- Study dates
- Feb 2014to Dec 2019
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects > 18 years < 65 of age
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must be considered a potential candidate for a major hepatic surgical procedure.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
- There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases confined to the Liver (Histologic confirmation of hepatic metastasis is not required.). The liver metastases must have been determined by a hepatic surgeon approved to participate in the study to be unresectable based on at least one of the following criteria: All of the liver metastases can not be resected (and/or ablated) with negative margins, i.e., lesion(s) located in an area that would result in the resection of all of the hepatic veins or the main portal vein or the right and left hepatic arteries or the common bile duct; Complete resection and/or ablation would require greater than 60% of the liver parenchyma to be removed.
- Patients are eligible with any of the following: primary tumor and regional nodes resected with clear surgical margins and no evidence of extra-hepatic disease or; unresected primary tumor with plans to resect the primary tumor prior to study entry or; unresected primary tumor with plans to resect the primary tumor and the liver metastases in a single surgical procedure performed within 8 weeks after the last preoperative dose of chemotherapy/cetuximab or; unresected primary with plans to resect the primary tumor and the liver metastases in staged procedures performed within 8 weeks after the last preoperative dose of chemotherapy/cetuximab.
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- The colorectal primary tumor or metastatic tumor must be determined to be KRAS and NRAS wild-type.
- At least one measurable lesion in liver metastases according to according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
- No previous any systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy for metastatic disease for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
- Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
- Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥ 9g/ dL.
- Total bilirubin ≤1.5 x the upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
- Alkaline phosphatase limit ≤ 5x ULN.
- Amylase and lipase ≤ 1.5 x the ULN.
- Serum creatinine ≤ 1.5 x the ULN.
- Calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.
Who cannot join
- Any evidence of extra-hepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
- Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver (Patients who have only had an excisional biopsy are eligible).
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
- Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities.
- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.
- Uncontrolled hypertension. (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
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- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.
- Any evidence of active infection.
- Known history of human immunodeficiency virus (HIV) infection.
- Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
- History of bleeding diathesis or coagulopathy.
- Uncontrolled hypertension. (systolic blood pressure ﹥150 mmHg or diastolic pressure ﹥ 90 mmHg despite optimal medical management).
- History of interstitial pneumonitis or pulmonary fibrosis
- Pregnancy or lactation at the time of study entry.
- Any history of or currently known brain metastases.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study.
- Unresolved toxicity higher than CTCAE v. 4.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity ﹥ Grade 2.
- Active inflammatory bowel disease or other bowel disease causing chronic diarrhea
- Subjects with known allergy to the study drugs or to any of its excipients.
- Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
Trial locations and contacts
1 site in 1 country.
China1 site
Gastrointestinal Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510655
About this study
Official title: A Phase II Study to Evaluate the Surgical Conversion Rate in Patients Receiving FOLFOXIRI +/- Cetuximab for Unresectable Wild-Type KRAS/NRAS Colorectal Cancer With Metastases Confined to the Liver
PURPOSE:
A primary aim of phase II FOCULM study is to explore whether cetuximab in combination with FOLFOXIRI as first treatment could improve surgical conversion in patients with KRAS/NRAS wild-type, unresectable liver - only metastases of colorectal cancer. The first secondary aim is to evaluate the safety and tolerability of the chemotherapy of FOLFOXIRI plus Cetuximab targeted therapy regimen in this patient population.
Secondary aims include determination of objective response rate, progression free survival, quality of life and time to recurrence for patients undergoing complete resection and/or ablation of liver.
Read the detailed description
Patients will be randomized to two therapy groups:
Experimental arm A: Chemotherapy with FOLFOXIRI + Cetuximab Standard arm B: Chemotherapy with FOLFOXIRI
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- FOLFOXIRI + Cetuximab, FOLFOXIRI
- Keywords
- Colorectal cancer, Metastatic colorectal cancer, Liver metastases, Liver resection, Liver ablation, Conversion therapy, FOLFOXIRI, Cetuximab, Oxaliplatin, Irinotecan, Leucovorin
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXIRI + CetuximabDrug
Also called Cetuximab, Irinotecan, Oxaliplatin, Leucovorin
Cetuximab 500mg/m² + irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
FOLFOXIRIDrug
Also called Irinotecan, Oxaliplatin, Leucovorin, 5-Fluorouracil
Irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles
| Study group | Role | What they receive |
|---|---|---|
| A (FOLFOXIRI + Cetuximab) | Experimental | FOLFOXIRI + Cetuximab Receives: Drug: FOLFOXIRI + Cetuximab |
| B (FOLFOXIRI) | Active comparator | FOLFOXIRI Receives: Drug: FOLFOXIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
the percentage of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be completely resected and/or ablated with no evidence of residual malignant disease.
Measured: 8 months
Secondary outcomes (5)
Reported adverse events.
Number of patients with adverse events and severity according to NCI CTC 4.0
Measured: 8 months
Response rate
CR + PR rate according to RECIST
Measured: 8 months
Progression free survival
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Measured: 2 years
Time to recurrence
Time from date of complete resection and/or ablation of liver until first recurrence
Measured: 2 years
Quality of life (QLQ C30)
scores according to EORTC QLQ-C30 scoring manual
Measured: Every 2 weeks after the first treatment until 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
- Investigators
- Yanhong Deng, M.D., Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02063529
- Sponsor's protocol ID
- GIHSYSU05
- Acronym
- FOCULM
- Status last verified
- Mar 2020
- First submitted
- 8 Feb 2014
- Last updated
- 31 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Surgical Conversion Rate in Patients Receiving FOLFOXIRI +/- Cetuximab for Unresectable Wild-Type KRAS/NRAS Colorectal Cancer With Metastases Confined to the Liver
- ClinicalTrials.gov ID
- NCT02063529
- Acronym / sponsor ID
- FOCULM / GIHSYSU05
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal cancer, Metastatic colorectal cancer, Liver metastases, Liver resection, Liver ablation, Conversion therapy, FOLFOXIRI, Cetuximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 14 Feb 2014 (estimated)
- 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.
PURPOSE:
A primary aim of phase II FOCULM study is to explore whether cetuximab in combination with FOLFOXIRI as first treatment could improve surgical conversion in patients with KRAS/NRAS wild-type, unresectable liver - only metastases of colorectal cancer. The first secondary aim is to evaluate the safety and tolerability of the chemotherapy of FOLFOXIRI plus Cetuximab targeted therapy regimen in this patient population.
Secondary aims include determination of objective response rate, progression free survival, quality of life and time to recurrence for patients undergoing complete resection and/or ablation of liver.
Detailed description
Patients will be randomized to two therapy groups:
Experimental arm A: Chemotherapy with FOLFOXIRI + Cetuximab Standard arm B: Chemotherapy with FOLFOXIRI
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A (FOLFOXIRI + Cetuximab) | Experimental | Drug: FOLFOXIRI + CetuximabFOLFOXIRI + Cetuximab |
| B (FOLFOXIRI) | Active comparator | Drug: FOLFOXIRIFOLFOXIRI |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects > 18 years < 65 of age
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and must be considered a potential candidate for a major hepatic surgical procedure.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
- There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases confined to the Liver (Histologic confirmation of hepatic metastasis is not required.). The liver metastases must have been determined by a hepatic surgeon approved to participate in the study to be unresectable based on at least one of the following criteria: All of the liver metastases can not be resected (and/or ablated) with negative margins, i.e., lesion(s) located in an area that would result in the resection of all of the hepatic veins or the main portal vein or the right and left hepatic arteries or the common bile duct; Complete resection and/or ablation would require greater than 60% of the liver parenchyma to be removed.
Key exclusion criteria (22 listed)
- Any evidence of extra-hepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
- Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver (Patients who have only had an excisional biopsy are eligible).
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
- Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities.
- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.
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 |
|---|---|---|
| FOLFOXIRI + CetuximabAlso: Cetuximab, Irinotecan, Oxaliplatin, LeucovorinCetuximab 500mg/m² + irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles | Drug | A (FOLFOXIRI + Cetuximab) |
| FOLFOXIRIAlso: Irinotecan, Oxaliplatin, Leucovorin, 5-FluorouracilIrinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles | Drug | B (FOLFOXIRI) |
Primary outcome
the percentage of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be completely resected and/or ablated with no evidence of residual malignant disease.
Time frame: 8 months
5 secondary outcomes
Reported adverse events.
Time frame: 8 months
Response rate
Time frame: 8 months
Progression free survival
Time frame: 2 years
Time to recurrence
Time frame: 2 years
Quality of life (QLQ C30)
Time frame: Every 2 weeks after the first treatment until 6 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 31 Mar 2020.
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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.
Yanhong Deng, M.D. principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
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 FOLFOXIRI + Cetuximab and FOLFOXIRI in people with Metastatic Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
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 17 inclusion and 22 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 31 Mar 2020. 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 China. 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?
the percentage of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be completely resected and/or ablated with no evidence of residual malignant disease. (time frame: 8 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 31 Mar 2020.