Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination ChemotherapyPhase 2NCT03641976
A Study of Bevacizumab, Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (A-FOLFOXIRI) Compared With Bevacizumab, Infusional Fluorouracil, Leucovorin, and Irinotecan/Oxaliplatin (A-FOLFIRI/FOLFOX) as First-line Treatment for Metastatic Right-sided Colon Cancer
A Phase 2 study testing A-FOLFOXIRI and Arm II (A-FOLFOX/A-FOLFIRI) in people with Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy and Unresectable Metastatic Right-sided Colon Cancer, Stage IV, run by Yonsei University at 1 site in South Korea.
Trial summary
RATIONALE: Recently, the importance of prognosis according to the location of the primary tumor in colorectal cancer has been raised. In the CALGB / SWOG 80405 study published in 2016, the addition of bevacizumab or cetuximab to the first line FOLFIRI / FOLFOX in KRAS (codon 12, 13) wild type metastatic colorectal… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy, Unresectable Metastatic Right-sided Colon Cancer, Stage IV
- What is being tested?
- A-FOLFOXIRI and Arm II (A-FOLFOX/A-FOLFIRI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSouth Korea
- Study dates
- 3 Jan 2019to Jun 2024
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven diagnosis of unresectable recurrent or advanced stage IV right-sided colon cancer (The definition of the right colon cancer is confirmed by the colonoscopy result, the surgical report, or the image reading paper including CT, MRI, and PET CT. (cecum~splenic flexure))
- Not previously treated with chemotherapy for metastatic disease
- At least one measurable lesion according to RECIST criteria
- Age over 19 years old
- ECOG 0~2
- Life expectancy of at least 3 months
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- Adequate major organ functions
- ANC ≥ 1.5 x 109/L
- PLT ≥ 100 x 109/L
- Hb ≥ 9.0 g/dL (can be corrected by blood transfusion)
- Total bilirubin ≤ upper normal limit(UNL) * 1.5
- ALT , AST ≤ UNL * 3 (in case of liver metastasis, ALT , AST ≤ UNL * 5), alkaline phosphatase ≤ UNL *3 (in case of liver metastasis, ALP ≤ UNL * 5
- adequate renal function : corrected creatinine clearance by Cockcroft and Gault formula ≥ 30mL/min
- Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate 1 g of protein/24 hr.
- Written informed consent.
Who cannot join
- Previously treated with chemotherapy for metastatic disease
- Within 6 months after adjuvant chemotherapy
- Major surgical procedure within 28 days prior to study treatment start, or patients who have not fully recovered from major surgery
- Radiotherapy to target lesion within 4 weeks before the study (A 2-week washout is permitted for palliative radiation.)
- Has known uncontrolled active CNS metastases and/or carcinomatous meningitis
- Peripheral neuropathy CTCAE v4.03 ≥ grade 2
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- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Note: Participants with basal cell carcinoma of skin, squamous cell carcinoma of the skin, low grade thyroid cancer or carcinoma in situ (eg, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic systemic treatment and is allowed.
- Uncontrolled hypertension or clinically active cardiovascular disease: for example, cerebrovascular accident or transient ischemic attack, unstable angina, myocardial infarction within 24 weeks prior to randomization. Have symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
- Have significant bleeding disorders, or evidence of bleeding diathesis or coagulopathy
- Have had a significant bleeding episode from the gastrointestinal (GI) tract or lung
- Have a history of GI perforation and/or fistula, or intra-abdominal abscess within 24 weeks prior to randomization.
- Have a history of HNPCC syndrome or polyposis
- Have experienced any arterial thromboembolic event or ongoing treatment with anticoagulants for therapeutic purpose within 24 weeks prior to randomization.
- Has a known history of human immunodeficiency virus (HIV) infection
- Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment. For women of childbearing potential and men, agreement to remain abstinent or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drugs. Postmenopausal women is defined that : 1) must have been amenorrheic for at least 12 months, > 50 years old or 2) Age ≤ 50 years old and amenorrheic for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range (>40 mIU/mL), 3) prior bilateral oophorectomy
- Patients who are hypersensitive reaction to experimental drugs
- Patients who are hypersensitive to CHO cell products or other recombinant or humanized antibodies
- In case of contraindication of experimental drugs
- Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the patient is, in the investigator's opinion, not an appropriate candidate for the study.
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Yonsei Cancer Center, Severance Hospital, Yonsei University Health System
Seoul, 03722
Joong Bae Ahn, MD,PhD, 82-2-2228-8134, vvswm513@yuhs.ac
About this study
Official title: A Randomized, Open-label, Multicenter Phase II Study of Bevacizumab, Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (A-FOLFOXIRI) Compared With Bevacizumab, Infusional Fluorouracil, Leucovorin, and Irinotecan/Oxaliplatin (A-FOLFIRI/FOLFOX) as First-line Treatment for Metastatic Right-sided Colon Cancer
RATIONALE: Recently, the importance of prognosis according to the location of the primary tumor in colorectal cancer has been raised. In the CALGB / SWOG 80405 study published in 2016, the addition of bevacizumab or cetuximab to the first line FOLFIRI / FOLFOX in KRAS (codon 12, 13) wild type metastatic colorectal cancer (mCRC) patients did not show a significant difference between overall survival (OS) and progression free survival (PFS) in both groups. Alan P. Venook et al. published a follow-up subgroup analysis on the effect of primary tumor location at 2016 ASCO. In the treatment group with cetuximab, the difference in treatment effect was significant according to the primary tumor location. The right colon cancer showed a poor prognosis for cetuximab treatment. (PFS: 7.8 vs 12.4 months, HR 1.56, p <0.0001 / OS: 16.7 vs 36.0months, HR 1.87, P <0.0001).
Therefore, the investigators propose a phase II trial for the efficacy evaluation of bevacizumab-FOLFOXIRI and bevacizumab-FOLFIRI or FOLFOX treatment in patients with poor prognosis of unresectable right-sided colorectal cancer.
Read the detailed description
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.
Arm I (A-FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
Arm II (A-FOLFOX/FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, fluorouracil IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
In both arms, treatment repeats every 2 weeks for up to 12 courses. After the 12 cycle treatment finished, investigator decides whether to keep the study drug. Treatment continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. If treatment with oxaliplatin or irinotecan is difficult due to side effects, treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity.
Patients undergo serum extraction and blood sample collection periodically for genomic, ctDNA and translational study. Patients also undergo collection of tumoral sections from paraffin embedded primary and/or metastatic lesions periodically for immunohistochemical analyses.
After completion of study treatment, patients are followed every 6 months for survival and other treatments.
- Conditions
- Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy, Unresectable Metastatic Right-sided Colon Cancer, Stage IV
- Being tested
- A-FOLFOXIRI, Arm II (A-FOLFOX/A-FOLFIRI)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A-FOLFOXIRIDrug
Arm I (A-FOLFOXIRI)
Biological: bevacizumab Given IV
Drug: fluorouracil Given IV
Drug: irinotecan hydrochloride Given IV
Drug: leucovorin calcium Given IV
Drug: oxaliplatin Given IV
Arm II (A-FOLFOX/A-FOLFIRI)Drug
Arm II (A-FOLFOX/A-FOLFIRI)
Biological: bevacizumab Given IV
Drug: fluorouracil Given IV
Drug: irinotecan hydrochloride Given IV
Drug: leucovorin calcium Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (A-FOLFOXIRI) | Experimental | Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Receives: Drug: A-FOLFOXIRI |
| Arm II (A-FOLFOX/A-FOLFIRI) | Active comparator | Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, fluorouracil IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. Receives: Drug: Arm II (A-FOLFOX/A-FOLFIRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month PFS rate (%)
To compare the 6-month progression free survival (PFS) rate (%) of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV (A-FOLFOXIRI regimen) to bevacizumab in combination with oxaliplatin or irinotecan and infusional 5FU/LV (A-FOLFOX/A-FOLFIRI regimen) in not previously treated, unresectable stage IV right-sided colon cancer
Measured: 6 months
Secondary outcomes (4)
overall survival(OS)
To compare the overall survival (OS) between treatment arms
Measured: 4 years
progression free survival(PFS)
To compare the progression free survival (PFS) between treatment arms
Measured: 4 years
adverse events
To evaluate the safety profile including long-term adverse events between treatment arms
Measured: 4 years
surrogate markers predictive of survival: ctDNA
To evaluate the correlation between 6-month PFS rate(%) and change in ctDNA
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start3 Jan 2019
- Primary completionJun 2024 (estimated)
- Study completionJun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination ChemotherapyStudies of the same condition, open and under way.
- More trials run by Yonsei 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03641976
- Sponsor's protocol ID
- 4-2018-0460
- Status last verified
- Oct 2020
- First submitted
- 20 Aug 2018
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Multicenter Phase II Study of Bevacizumab, Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (A-FOLFOXIRI) Compared With Bevacizumab, Infusional Fluorouracil, Leucovorin, and Irinotecan/Oxaliplatin (A-FOLFIRI/FOLFOX) as First-line Treatment for Metastatic Right-sided Colon Cancer
- ClinicalTrials.gov ID
- NCT03641976
- Acronym / sponsor ID
- 4-2018-0460
- Conditions
- Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy, Unresectable Metastatic Right-sided Colon Cancer, Stage IV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 3 Jan 2019 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 22 Aug 2018 (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.
RATIONALE: Recently, the importance of prognosis according to the location of the primary tumor in colorectal cancer has been raised. In the CALGB / SWOG 80405 study published in 2016, the addition of bevacizumab or cetuximab to the first line FOLFIRI / FOLFOX in KRAS (codon 12, 13) wild type metastatic colorectal cancer (mCRC) patients did not show a significant difference between overall survival (OS) and progression free survival (PFS) in both groups. Alan P. Venook et al. published a follow-up subgroup analysis on the effect of primary tumor location at 2016 ASCO. In the treatment group with cetuximab, the difference in treatment effect was significant according to the primary tumor location. The right colon cancer showed a poor prognosis for cetuximab treatment. (PFS: 7.8 vs 12.4 months, HR 1.56, p <0.0001 / OS: 16.7 vs 36.0months, HR 1.87, P <0.0001).
Therefore, the investigators propose a phase II trial for the efficacy evaluation of bevacizumab-FOLFOXIRI and bevacizumab-FOLFIRI or FOLFOX treatment in patients with poor prognosis of unresectable right-sided colorectal cancer.
Detailed description
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-2), prior adjuvant chemotherapy (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.
Arm I (A-FOLFOXIRI): Patients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
Arm II (A-FOLFOX/FOLFIRI): Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, fluorouracil IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1.
In both arms, treatment repeats every 2 weeks for up to 12 courses. After the 12 cycle treatment finished, investigator decides whether to keep the study drug. Treatment continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity. If treatment with oxaliplatin or irinotecan is difficult due to side effects, treatment with bevacizumab, fluorouracil, and leucovorin calcium continues in the absence of disease progression, withdrawal consent, or unacceptable toxicity.
Patients undergo serum extraction and blood sample collection periodically for genomic, ctDNA and translational study. Patients also undergo collection of tumoral sections from paraffin embedded primary and/or metastatic lesions periodically for immunohistochemical analyses.
After completion of study treatment, patients are followed every 6 months for survival and other treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (A-FOLFOXIRI) | Experimental | Drug: A-FOLFOXIRIPatients receive irinotecan hydrochloride IV over 1 hour, oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. |
| Arm II (A-FOLFOX/A-FOLFIRI) | Active comparator | Drug: Arm II (A-FOLFOX/A-FOLFIRI)Patients receive irinotecan hydrochloride IV over 1 hour (or oxaliplatin IV over 2 hours), leucovorin calcium IV over 2 hours, fluorouracil IV bolus, and bevacizumab IV on day 1. Patients also receive fluorouracil IV continuously over 48 hours beginning on day 1. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven diagnosis of unresectable recurrent or advanced stage IV right-sided colon cancer (The definition of the right colon cancer is confirmed by the colonoscopy result, the surgical report, or the image reading paper including CT, MRI, and PET CT. (cecum~splenic flexure))
- Not previously treated with chemotherapy for metastatic disease
- At least one measurable lesion according to RECIST criteria
- Age over 19 years old
- ECOG 0~2
Key exclusion criteria (21 listed)
- Previously treated with chemotherapy for metastatic disease
- Within 6 months after adjuvant chemotherapy
- Major surgical procedure within 28 days prior to study treatment start, or patients who have not fully recovered from major surgery
- Radiotherapy to target lesion within 4 weeks before the study (A 2-week washout is permitted for palliative radiation.)
- Has known uncontrolled active CNS metastases and/or carcinomatous meningitis
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 |
|---|---|---|
| A-FOLFOXIRIArm I (A-FOLFOXIRI) Biological: bevacizumab Given IV Drug: fluorouracil Given IV Drug: irinotecan hydrochloride Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV | Drug | Arm I (A-FOLFOXIRI) |
| Arm II (A-FOLFOX/A-FOLFIRI)Arm II (A-FOLFOX/A-FOLFIRI) Biological: bevacizumab Given IV Drug: fluorouracil Given IV Drug: irinotecan hydrochloride Given IV Drug: leucovorin calcium Given IV | Drug | Arm II (A-FOLFOX/A-FOLFIRI) |
Primary outcome
6-month PFS rate (%)
Time frame: 6 months
To compare the 6-month progression free survival (PFS) rate (%) of bevacizumab in combination with oxaliplatin, irinotecan and infusional 5FU/LV (A-FOLFOXIRI regimen) to bevacizumab in combination with oxaliplatin or irinotecan and infusional 5FU/LV (A-FOLFOX/A-FOLFIRI regimen) in not previously treated, unresectable stage IV right-sided colon cancer
4 secondary outcomes
overall survival(OS)
Time frame: 4 years
progression free survival(PFS)
Time frame: 4 years
adverse events
Time frame: 4 years
surrogate markers predictive of survival: ctDNA
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Individual participant dataSharing planned: Undecided
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.
Yonsei Cancer Center, Severance Hospital, Yonsei University Health System
Seoul, South Korea
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 A-FOLFOXIRI and Arm II (A-FOLFOX/A-FOLFIRI) in people with Unresectable Metastatic Right-sided Colon Cancer Starting First-line Combination Chemotherapy and Unresectable Metastatic Right-sided Colon Cancer, Stage IV, run by Yonsei University at 1 site in South Korea.
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 21 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: status not confirmed, as of the sponsor's last update on 19 Oct 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 South Korea. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month PFS rate (%) (time frame: 6 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 19 Oct 2020.