Colorectal Cancer MetastaticPhase 1/2NCT04790448
Efficacy of VIC Regimen in BRAF Mutant Metastatic Colorectal Cancer
A Phase 1/2 study testing Cetuximab, Irinotecan and Vemurafenib in people with Colorectal Cancer Metastatic, run by Sun Yat-sen University at 1 site in China.
Trial summary
This prospective, multicenter, single arm clinical trial was designed to evaluate the efficacy and safety of Vemurafenib in combination with Irinotecan and Cetuximab in the treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Cetuximab, Irinotecan and Vemurafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteChina
- Study dates
- 27 Jul 2020to 31 Dec 2021
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of metastatic colorectal cancer
- Histopathological or ctDNA analysis positive for BRAF V600E mutant
- Patients must have had at least undergone one first line treatment with FOLFOX or FOLFIRI or FOLFOXIRI±Bevacizumab before disease progression.
- Measurable and assessable disease according to RECIST 1.1 criteria
- Adequate hematologic function (Platelet>90×109/L; White blood cells>3.0×109/L; Neutrophils>1.5×109/L; Hb>10.0g/100ml)
- Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminase ≤5 times ULN
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- No ascites, normal coagulation function, albumin ≥35g/L
- Child-Pugh class A
- Serum creatinine is less than the upper limit of normal (ULN), or calculated creatinine clearance rate> 50ml/min (using Cockcroft-Gault equation)
- ECOG performance status of grade 0-2
- Life expectancy> 3 months
- Patients must provide a signed Informed Consent Form
- Patients must have good compliance till the end of this study
Who cannot join
- Patients with KRAS and NRAS mutations
- Previously received anti-EGFR monoclonal antibodies or EGFR inhibitors, BRAF inhibitors (with the exception of regorafenib)
- Patients with known contraindications to receiving cetuximab or irinotecan at the planned dose
- Patients with retinal vein occlusion or have current risk factors for retinal vein occlusion (for example, uncontrolled glaucoma or ocular hypertension)
- History of acute or chronic pancreatitis
- History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive drugs or surgery) within 12 months prior to enrollment
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- Gastrointestinal diseases that may greatly affect the absorption of Vimurafenib (for example, ulcer disease, uncontrolled vomiting, malabsorption syndrome, small bowel resection and reduced intestinal absorption)
- Neuromuscular diseases associated with elevated CK (eg, inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
- Patients with any residual CTCAE ≥ Grade 2 toxicity from previous anti-tumor therapy (excluding hair loss or neuropathy of Grade 2 and above)
- History of HIV infection
- Active hepatitis B or C infection
- History of Gilbert syndrome
- Interstitial pneumonia or widespread symptomatic interstitial pulmonary fibrosis
- Serious uncontrollable systemic complications such as infection or diabetes
- Clinically serious cardiovascular diseases such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), hypertension that cannot be controlled after proper medical treatment, unstable angina pectoris, congestion Heart failure (NYHA 2-4), arrhythmia requiring medication
- History of or showing signs of a central nervous system disease (such as primary brain tumors, epilepsy that cannot be controlled by standard treatment, any brain metastases or history of stroke)
- Patients must not suffer from other uncontrolled concurrent diseases, including but not limited to hypertensive crisis or hypertensive encephalopathy, active bleeding, uncontrolled infections/diseases, uncontrolled non-malignant medical diseases or use research therapies that could worsen non-malignant medical diseases or mental illnesses/social conditions
- No history of other malignant tumors in the past 5 years (excluding skin basal cell carcinoma and/or cervical carcinoma in situ and/or thyroid cancer after radical resection)
- Patients allergic to any drugs in the study
- Patients must not be pregnant or breastfeeding
- Women of reproductive potential (<2 years after the last menstruation) who have not used or refused to use effective non- hormonal contraceptive methods (intrauterine contraceptive ring, barrier contraception combined with spermicidal gel or sterilization) or Men wanting to keep their reproductive potential.
- Patients unable or unwilling to comply with the protocol of this clinical trial
- Existence of any other diseases, dysfunction caused by metastatic lesions, or suspicious diseases found during physical examination, which may indicate contraindications to the use of the drugs in this study or could bring about high risk of treatment-related complications to the patient
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase Ia/II, Single Arm Trial on the Efficacy of Vemurafenib in Combination With Irinotecan and Cetuximab in BRAF V600E-Mutant Metastatic Colorectal Cancer
This prospective, multicenter, single arm clinical trial was designed to evaluate the efficacy and safety of Vemurafenib in combination with Irinotecan and Cetuximab in the treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer.
Read the detailed description
PRIMARY OBJECTIVES:
To evaluate the Overall Response Rate (ORR) of v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutant metastatic colorectal cancer patients treated with Vemurafenib in combination with Irinotecan and Cetuximab (VIC regimen).
SECONDARY OBJECTIVES:
To evaluate the Progression Free Survival (PFS), Overall Survival (OS), safety and toxicity of VIC regimen in the treatment of BRAF V600E mutant colon cancer.
EXPLORATORY OBJECTIVES:
Mechanism of primary and secondary resistance to VIC regimen in the treatment of BRAF V600E mutant colon cancer.
OUTLINE:
Patients receive Cetuximab and Irinotecan intravenously on day 1 and Vemurafenib orally (PO) twice daily (BID) on days 1 to 14. Courses are repeated every 2 weeks in the absence of disease progression or unacceptable toxicity.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Cetuximab, Irinotecan, Vemurafenib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called C225, Erbitux
Route of administration: Intravenous
IrinotecanDrug
Also called CPT-11, Camptothecin-11, Camptosar
Route of administration: Intravenous
VemurafenibDrug
Also called Zelboraf
Route of administration: Oral
| Study group | Role | What they receive |
|---|---|---|
| VIC regimen | Experimental | Patients will receive VIC regimen every 2 weeks:
Cetuximab 500mg/m2 IV on Day 1; Irinotecan 180mg/m2 IV on Day 1 (If patient carries UGT*28 7/7 or UGT*6 A/A or UGT*28 6/7 and UGT*6 A/G variants, use Irinotecan IV 150mg/m2 instead); Vemurafenib PO BID on Days 1 to 14 (Dosage: 480mg; 720mg; 960mg, determined by the maximum tolerated dose (MTD) in Phase Ia trial). Receives: Drug: Cetuximab; Drug: Irinotecan; Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate from the date of first drug administration until the date of first documented progression or date of death, whichever came first.
The proportion of patients who achieved a complete or partial response as their best overall response based on RECIST v1.1 criteria
Measured: up to 17 months
Secondary outcomes (3)
Progression free survival from the date of first drug administration until the date of first documented progression or date of death, whichever came first.
The length of time during and after the treatment of the disease, that a patient lives with the disease without its aggravation
Measured: up to 17 months
Overall Survival from the date of first drug administration until the date of death from any cause.
The length of time from the start of treatment that patients diagnosed are still alive
Measured: up to 17 months
Number of patients with adverse events and severity according to NCI CTCAE v5.0
Summary of the Adverse events experienced during treatment related to the drug used in this study
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start27 Jul 2020
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yuhong Li, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04790448
- Sponsor's protocol ID
- VIC-BRAFMT-mCRC
- Status last verified
- Feb 2023
- First submitted
- 7 Mar 2021
- Last updated
- 15 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ia/II, Single Arm Trial on the Efficacy of Vemurafenib in Combination With Irinotecan and Cetuximab in BRAF V600E-Mutant Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04790448
- Acronym / sponsor ID
- VIC-BRAFMT-mCRC
- Conditions
- Colorectal Cancer Metastatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 10 Mar 2021 (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.
This prospective, multicenter, single arm clinical trial was designed to evaluate the efficacy and safety of Vemurafenib in combination with Irinotecan and Cetuximab in the treatment of BRAF V600E-Mutant Metastatic Colorectal Cancer.
Detailed description
PRIMARY OBJECTIVES:
To evaluate the Overall Response Rate (ORR) of v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutant metastatic colorectal cancer patients treated with Vemurafenib in combination with Irinotecan and Cetuximab (VIC regimen).
SECONDARY OBJECTIVES:
To evaluate the Progression Free Survival (PFS), Overall Survival (OS), safety and toxicity of VIC regimen in the treatment of BRAF V600E mutant colon cancer.
EXPLORATORY OBJECTIVES:
Mechanism of primary and secondary resistance to VIC regimen in the treatment of BRAF V600E mutant colon cancer.
OUTLINE:
Patients receive Cetuximab and Irinotecan intravenously on day 1 and Vemurafenib orally (PO) twice daily (BID) on days 1 to 14. Courses are repeated every 2 weeks in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VIC regimen | Experimental | Drug: Cetuximab, Drug: Irinotecan, Drug: VemurafenibPatients will receive VIC regimen every 2 weeks: Cetuximab 500mg/m2 IV on Day 1; Irinotecan 180mg/m2 IV on Day 1 (If patient carries UGT*28 7/7 or UGT*6 A/A or UGT*28 6/7 and UGT*6 A/G variants, use Irinotecan IV 150mg/m2 instead); Vemurafenib PO BID on Days 1 to 14 (Dosage: 480mg; 720mg; 960mg, determined by the maximum tolerated dose (MTD) in Phase Ia trial). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed diagnosis of metastatic colorectal cancer
- Histopathological or ctDNA analysis positive for BRAF V600E mutant
- Patients must have had at least undergone one first line treatment with FOLFOX or FOLFIRI or FOLFOXIRI±Bevacizumab before disease progression.
- Measurable and assessable disease according to RECIST 1.1 criteria
- Adequate hematologic function (Platelet>90×109/L; White blood cells>3.0×109/L; Neutrophils>1.5×109/L; Hb>10.0g/100ml)
Key exclusion criteria (23 listed)
- Patients with KRAS and NRAS mutations
- Previously received anti-EGFR monoclonal antibodies or EGFR inhibitors, BRAF inhibitors (with the exception of regorafenib)
- Patients with known contraindications to receiving cetuximab or irinotecan at the planned dose
- Patients with retinal vein occlusion or have current risk factors for retinal vein occlusion (for example, uncontrolled glaucoma or ocular hypertension)
- History of acute or chronic pancreatitis
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 |
|---|---|---|
| CetuximabAlso: C225, ErbituxRoute of administration: Intravenous | Drug | VIC regimen |
| IrinotecanAlso: CPT-11, Camptothecin-11, CamptosarRoute of administration: Intravenous | Drug | VIC regimen |
| VemurafenibAlso: ZelborafRoute of administration: Oral | Drug | VIC regimen |
Primary outcome
Overall response rate from the date of first drug administration until the date of first documented progression or date of death, whichever came first.
Time frame: up to 17 months
The proportion of patients who achieved a complete or partial response as their best overall response based on RECIST v1.1 criteria
3 secondary outcomes
Progression free survival from the date of first drug administration until the date of first documented progression or date of death, whichever came first.
Time frame: up to 17 months
Overall Survival from the date of first drug administration until the date of death from any cause.
Time frame: up to 17 months
Number of patients with adverse events and severity according to NCI CTCAE v5.0
Time frame: up to 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 15 Feb 2023.
- Individual participant dataSharing planned: Undecided
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CRC
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cetuximab, Irinotecan and Vemurafenib in people with Colorectal Cancer Metastatic, 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 13 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 15 Feb 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Overall response rate from the date of first drug administration until the date of first documented progression or date of death, whichever came first. (time frame: up to 17 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 15 Feb 2023.