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AzTrials

Metastatic Colorectal CancerPhase 2NCT05103020

Phase II Study Comparing Conversion Rate to Surgery With Hepatic Arterial Infusion Chemotherapy to Systemic Chemotherapy in Patients With Non Resectable Liver-only Colorectal Metastases

A Phase 2 study testing intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks and IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks in people with Metastatic Colorectal Cancer, run by Yonsei University at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10 - 15% of CRLM are initially considered resectable. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks and IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteSouth Korea
Study dates
1 Nov 2021to Mar 2025
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 confirmed colorectal cancer (CRC), and radiologic or histologic proof of liver metastasis.
  • Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria):
  • Upfront R0/R1 resection of all CRLM (that leaves at least two adequately perfused and drained segments) is not possible
  • Liver metastases in contact with major vessels of the remnant liver which would require resection of the vessel for an R0 resection (i.e., tumor involvement of main portal right and left portal veins, of the three main hepatic veins, or of the retrohepatic vena cava)
  • At least one measurable liver metastasis according to the RECIST v1.1
  • Age ≥18 years
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy of at least 3 months
  • Normal liver function International normalized ratio (INR) <1.5 ULN
  • Neutrophils >1500/mm³
  • Platelet >100 x 109/L (transfusion allowed)
  • Hemoglobin >9 g/dL (transfusion allowed)
  • Bilirubin <1.5 times the upper limit of normal values (ULN)
  • Aminotransferases <5 ULN, alkaline phosphatase <5 ULN
  • Calculated creatinine clearance >30 mL/min (Cockcroft and Gault formula)
  • Urine dipstick for proteinuria of less than 1+ is required within 7 days prior to study entry; if urine dipstick is >= 2+ then a 24 hour urine for protein must demonstrate =< 1 gm of protein in 24 hours to allow participation in the study; NOTE: Urinalysis is also acceptable
  • Informed consent signed by the patient or his/her legal representative

Who cannot join

  • Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review. Definitive anatomical contraindication to complete surgical resection (any of the following criteria):
  • More than two lesions in all liver segments
  • Bilobar liver metastasis and more than three lesions >3 cm in the hepatic lobe the least affected (i.e. the future remnant liver)
  • Bilobar liver metastasis and disease liver extend >50%
  • Extrahepatic tumor disease (except ≤3 lung nodules <10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms)
  • Major surgical procedure within 28 days prior to study treatment start, or patients who have not fully recovered from major surgery
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  • 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
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Note: Participants with (A) basal cell carcinoma of skin, (B) squamous cell carcinoma of the skin, (C) 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.

Dai Hoon Han, MD, PhD contact

+82-2-2228-2100

DHHAN@yuhs.ac

Joong Bae Ahn, M.D, Ph.D contact

+82-2-2228-0400

vvswm513@yuhs.ac

South Korea1 site, 1 recruiting

  • Severance Hospital, Yonsei University Health System

    Seoul

    Dai Hoon Han, MD, PhD, +82-2-2228-2100, DHHAN@yuhs.ac

    Joong Bae Ahn, M.D., Ph.D., +82-2-2228-0400, vvswm513@yuhs.ac

    Recruiting

Other trials in South Korea

About this study

Official title: A Randomized, Open-label, Single-center Phase II Study Comparing Conversion Rate to Surgery With Hepatic Arterial Infusion Chemotherapy to Systemic Chemotherapy in Patients With Non Resectable Liver-only Colorectal Metastases

Approximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10 - 15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as the first-line treatment in patients with unresectable CRLM.

Being tested
intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks, IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeksDrug

    Bevacizumab : 5mg/kg IV over 30min, day 1 or Cetuximab : 500 mg/m2 IV over 2-hr, day 1 Oxaliplatin : HAI 100mg/m2 IV over 2-hr, day 1 Leucovorin : 400mg/m2 IV over 2-hr, day 1 5-Fluorouracil : 2400mg/m2 infusion for 46-h Irinotecan : 180mg/m2 IV over 1.5-hr, day 1

  • IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeksDrug

    Bevacizumab : 5mg/kg IV over 30min, day 1 or Cetuximab : 500 mg/m2 IV over 2-hr, day 1 Irinotecan : 180mg/m2 IV over 1.5-hr, day 1 Leucovorin : 400mg/m2, IV over 2-hr, day 1 5-Fluorouracil : 400mg/m2 IV bolus, day 1 5-Fluorouracil : 2400mg/m2, infusion for 46-h

Study groups in NCT05103020
Study groupRoleWhat they receive
HAI oxaliplatin and systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)ExperimentalHAI-oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab)
Receives: Drug: intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks
Systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)Active comparatorIV FOLFIRI+ target agent (bevacizumab or cetuximab)
Receives: Drug: IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. curative-intent resection rate

    The primary study objective is to compare the rate of conversion to resectable liver after HAI plus sys-CT and sys-CT alone in colorectal cancer patients with previously untreated and unresectable liver metastases at diagnosis. Randomized patients will receive either chemotherapy combining HAI oxaliplatin plus systemic FOLFIRI and targeted therapy (bevacizumab or cetuximab) or systemic FOLFIRI and targeted therapy (bevacizumab or cetuximab).

    Measured: Every 4 cycles of chemotherapy (approximately 24 months) (each cycle is 2weeks)

Secondary outcomes (4)

  1. Overall survival

    Measured: Every 8 weeks from date of first treatment until the date of death from any cause, assessed approximately up to 24 months

  2. Progression-free survival

    Measured: Every 8 weeks from date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed approximately up to 24 months

  3. Toxicity profile

    Overall safety profile verified as relevance of adverse events and laboratory abnormality in the study and grades granted based on (USA National Cancer Center) Common Terminology Criteria for Adverse Events such as the type, frequency and severity (CTCAE), v4.0.

    Measured: Every 4 weeks from date of first treatment until date of last treatment up to 24 months

  4. Overall response rate (ORR)

    Overall objective response rate (ORR) is the best response rate stipulated as complete response (CR) or partial response (PR) (target lesion and tumor response defined according to RECIST guideline version 1.1) and identified as percentage of the confirmed patients.

    Measured: Every 8 weeks from date of first treatment until date of last treatment up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2021
  2. Study start1 Nov 2021 (estimated)
  3. Primary completionMar 2023 (estimated)
  4. Study completionMar 2025 (estimated)

Resources

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
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05103020
Sponsor's protocol ID
4-2021-0034
Status last verified
Nov 2021
First submitted
14 Oct 2021
Last updated
2 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kim JS, Kim H, Lee SY, Han YD, Han K, Min BS, Kim MD, Won JY, Beom SH, Shin SJ, Kim HS, Han DH, Ahn JB. Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study - (NCT05103020) - study protocol. BMC Cancer. 2023 Jul 22;23(1):691. doi: 10.1186/s12885-023-11085-w.

    PubMed 37481515

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks and IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks in people with Metastatic Colorectal Cancer, 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 17 inclusion and 24 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 2 Nov 2021. 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?

Contact Dai Hoon Han, MD, PhD (+82-2-2228-2100, DHHAN@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

curative-intent resection rate (time frame: Every 4 cycles of chemotherapy (approximately 24 months) (each cycle is 2weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05103020, which also lists 1 linked publication.

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 2 Nov 2021.

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