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

NCT05103020 | Unknown Phase 2

• 1 other identifier: 4-2021-0034
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (4)

• Overall survival

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

• Progression-free survival

  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

• Toxicity profile

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

• Overall response rate (ORR)

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

Study Arms (2)

HAI oxaliplatin and systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)

EXPERIMENTAL

HAI-oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab)

Drug: intra-arterial oxaliplatin + Systemic FOLFIRI + target agent (bevacizumab or cetuximab) every 2 weeks

Systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)

ACTIVE COMPARATOR

IV FOLFIRI+ target agent (bevacizumab or cetuximab)

Drug: IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks

Interventions

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

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

HAI oxaliplatin and systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)

IV FOLFIRI+ target agent (bevacizumab or cetuximab) every 2 weeks DRUG

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

Systemic FOLFIRI plus targeted therapy (bevacizumab or cetuximab)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance Hospital, Yonsei University Health System

Seoul, South Korea

RECRUITING

Related Publications (1)

• 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.

  PMID: 37481515 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dai Hoon Han, M.D, Ph.D

  Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

• Joong Bae Ahn, M.D, Ph.D

  Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 2, 2021
• Study Start: November 1, 2021
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2025
• Last Updated: November 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)