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FOLFOXIRI With or Without Cetuximab as First-line Treatment of Patients With Non-resectable Liver - Only Metastatic Colorectal Cancer

NCT02063529

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FOLFOXIRI With or Without Cetuximab as First-line Treatment of Patients With Non-resectable Liver - Only Metastatic Colorectal Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GIHSYSU05
  • NCT ID: NCT02063529

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
FOLFOXIRI + CetuximabCetuximab, Irinotecan, Oxaliplatin, Leucovorin, 5-FluorouracilA (FOLFOXIRI + Cetuximab)
FOLFOXIRIIrinotecan, Oxaliplatin, Leucovorin, 5-FluorouracilB (FOLFOXIRI)

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
A (FOLFOXIRI + Cetuximab)ExperimentalFOLFOXIRI + Cetuximab
  • FOLFOXIRI + Cetuximab
B (FOLFOXIRI)Active ComparatorFOLFOXIRI
  • FOLFOXIRI

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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.

        Exclusion Criteria:

          -  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).

          -  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.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Reported adverse events.
Time Frame:8 months
Safety Issue:
Description:Number of patients with adverse events and severity according to NCI CTC 4.0
Measure:Response rate
Time Frame:8 months
Safety Issue:
Description:CR + PR rate according to RECIST
Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Measure:Time to recurrence
Time Frame:2 years
Safety Issue:
Description:Time from date of complete resection and/or ablation of liver until first recurrence
Measure:Quality of life (QLQ C30)
Time Frame:Every 2 weeks after the first treatment until 6 months
Safety Issue:
Description:scores according to EORTC QLQ-C30 scoring manual

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sun Yat-sen University

Trial Keywords

  • Colorectal cancer
  • Metastatic colorectal cancer
  • Liver metastases
  • Liver resection
  • Liver ablation
  • Conversion therapy
  • FOLFOXIRI
  • Cetuximab
  • Oxaliplatin
  • Irinotecan
  • Leucovorin

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