Clinical Trials /

Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With RAS Wild-Type Locally Advanced or Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

NCT02292758

Description:

This randomized phase II trial studies how well irinotecan and cetuximab with or without bevacizumab work in treating patients with RAS wild-type colorectal cancer that has spread to other places in the body and cannot be removed by surgery. Irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving irinotecan and cetuximab with or without bevacizumab may work betting in treating patients with colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase II Trial of <span class="go-doc-concept go-doc-intervention">Irinotecan</span>, <span class="go-doc-concept go-doc-intervention">Cetuximab</span>, and <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> Compared With <span class="go-doc-concept go-doc-intervention">Irinotecan</span>, <span class="go-doc-concept go-doc-intervention">Cetuximab</span>, and <span class="go-doc-concept go-doc-intervention">Placebo</span> in <span class="go-doc-concept go-doc-biomarker">KRAS</span>-Wildtype, <span class="go-doc-concept go-doc-intervention">Irinotecan</span>-Refractory, Metastatic <span class="go-doc-concept go-doc-disease">Colorectal Cancer</span>

Title

  • Brief Title: Phase II Trial of Irinotecan, Cetuximab, and Bevacizumab Compared With Irinotecan, Cetuximab, and Placebo in KRAS-Wildtype, Irinotecan-Refractory, Metastatic Colorectal Cancer
  • Official Title: A Randomized, Double-blind, Placebo-Controlled Phase II Trial of Irinotecan, Cetuximab, and Bevacizumab Compared With Irinotecan, Cetuximab, and Placebo in KRAS-Wildtype, Irinotecan-Refractory, Metastatic Colorectal Cancer
  • Clinical Trial IDs

    NCT ID: NCT02292758

    ORG ID: RU021302I

    Trial Conditions

    Metastatic Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Bevacizumab Bevacizumab and irinotecan and cetuximab
    Irinotecan Bevacizumab and irinotecan and cetuximab, Placebo and irinotecan and cetuximab
    Cetuximab Bevacizumab and irinotecan and cetuximab, Placebo and irinotecan and cetuximab

    Trial Purpose

    The purpose of this research study is to see if cancer will respond better to a combination
    of irinotecan and cetuximab with or without bevacizumab

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Bevacizumab and irinotecan and cetuximab Active Comparator Participant will receive cetuximab, bevacizumab and irinotecan by a needle through a vein in your arm (IV infusion) on day 1 of each cycle. The 14 day period of time is called a cycle. It will take 3-4 hours to give all three drugs. Bevacizumab, Irinotecan, Cetuximab
    Placebo and irinotecan and cetuximab Placebo Comparator Participant will receive cetuximab, placebo and irinotecan by a needle through a vein in your arm (IV infusion) on day 1 of each cycle. The 14 day period of time is called a cycle. It will take 3-4 hours to give all three drugs. Irinotecan, Cetuximab

    Eligibility Criteria

    Inclusion Criteria:

    - Metastatic or locally advanced (unresectable) colorectal cancer with histological
    confirmation of adenocarcinoma.

    - Age 18 years of age. Note: Because no dosing or adverse event data are currently
    available on the use of cetuximab or bevacizumab in subjects <18 years of age,
    children are excluded from this study.

    - Measurable disease as defined in Section 11.0.

    - KRAS wild-type tumor (codons 12 and 13).

    Note: Evidence of EGFR expression in the tumor is not required.

    Note: Although testing for other RAS mutations is not required, a known mutation in other
    regions of KRAS, NRAS, or HRAS is exclusionary.

    - Previous failure of at least one fluoropyrimidine- and irinotecan-containing
    chemotherapy regimen for metastatic disease.

    Note: Previous failure is defined as disease progression while receiving treatment or
    within 6 weeks after the last dose of irinotecan. Failure for this assessment is defined
    as any enlargement of measurable or assessable lesion(s) or the development of any new
    lesion. A rising tumor marker alone is not sufficient to define failure. Patients can
    have received irinotecan in any previous line of therapy.

    - Treatment with bevacizumab in at least one prior line of therapy for metastatic
    disease.

    - Negative serum or urine pregnancy test done 7 days prior to registration, for women
    of childbearing potential only.

    Note: Childbearing potential is defined as a female who has experienced menarche and who
    has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or
    bilateral oophorectomy) or who is not postmenopausal (defined as amenorrhea 12
    consecutive months; or women on hormone replacement therapy with documented serum follicle
    stimulating hormone level >35 mIU/mL). Women who are using oral, implanted, or injectable
    contraceptive hormones or mechanical products such as intrauterine device or barrier
    methods (diaphragm, condoms, spermicides) to prevent pregnancy, or who are practicing
    abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of
    childbearing potential.

    - ECOG Performance Status (PS): 0 or 1 (form available on the ACCRU member website at
    https://www.accru.org/accru/forms/NonProtocolSpecificForms/index.html).

    - Adequate organ and bone marrow function as defined below (see Section 3.19b)

    - The following laboratory values obtained 14 days prior to randomization.

    - Total serum bilirubin institutional upper limit of normal (ULN)

    - Absolute neutrophil count (ANC) 1500/mm3

    - Platelet count >100,000/mm3

    - Hemoglobin 9.0 g/dL (hemoglobin may be supported by transfusion)

    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.5 x ULN
    ( 5 x ULN for subjects with liver involvement of their cancer)

    - Creatinine within institutional limits of normal OR

    - creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
    institutional normal.

    - Urinary protein 1+

    - Patients discovered to have 2+ proteinuria must have a spot urine protein:creatinine
    ratio (UPCR) <1.0

    - Partial thromboplastin time (PTT) 1x institutional ULN and international normalized
    ratio (INR) 1.5, unless participant is on full dose anticoagulation therapy.
    Patients on full-dose anticoagulation are eligible if the following criteria are met:

    - Patient has an in-range INR (usually 2-3) on a stable dose of warfarin 14 days or
    is on a stable dose of low molecular weight heparin

    - Patient has no active bleeding or pathological condition that carries a high risk of
    bleeding (i.e., tumor involving major vessels or known varices)

    - Patients receiving anti-platelet agents are eligible. In addition, patients who are
    on daily prophylactic aspirin or anticoagulation for atrial fibrillation are
    eligible.

    - Life expectancy >3 months.

    - Willing to provide tissue and blood samples for mandatory correlative and research
    purposes (see Sections 6.0, 14.0 and 17.0).

    - Any major surgery or open biopsy completed 4 weeks prior to randomization.

    - Any minor surgery or core biopsy completed 1 week prior to randomization and patient
    must have fully recovered from the procedure.

    Note: Insertion of a vascular access device is not considered major or minor surgery.

    Exclusion Criteria:

    - Presence of any RAS mutation

    - Prior treatment with cetuximab or panitumumab.

    - Prior intolerance to irinotecan and/or bevacizumab despite dose reduction.

    - Known or suspected brain or central nervous system (CNS) metastases, or carcinomatous
    meningitis.

    Note: Participants with brain or CNS metastases are excluded from this clinical trial
    because of their poor prognosis and because they often develop progressive neurologic
    dysfunction that would confound the evaluation of neurologic and other adverse events.

    - Active, uncontrolled infection, including hepatitis B, hepatitis C.

    - Concurrent anti-cancer therapy, including chemotherapy agents, targeted agents, or
    biological agents not otherwise specified in this protocol.

    - Anti-cancer therapy 14 days prior to randomization.

    - Prior radiotherapy to >25% of bone marrow.

    Note: Standard rectal cancer chemoradiation will not exclude subject from study protocol.

    - Radiation therapy 2 weeks prior to randomization.

    - Any of the following, because this study involves agents whose genotoxic, mutagenic
    and teratogenic effects on the developing fetus and newborn are unknown:

    - Pregnant women

    - Nursing women

    - Men or women of childbearing potential who are unwilling to employ adequate
    contraception

    - Co-morbid systemic illnesses or other severe concurrent disease, history of any
    psychiatric or addictive disorder, or laboratory abnormality, which, in the judgment
    of the investigator, would make the patient inappropriate for entry into this study
    or interfere significantly with the proper assessment of safety and toxicity of the
    prescribed regimens.

    - Patients known to be HIV positive

    Note: HIV-positive individuals on combination antiretroviral therapy are ineligible
    because of the potential for pharmacokinetic interactions with irinotecan, cetuximab, and
    bevacizumab. In addition, these individuals are at increased risk of lethal infections
    when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in
    participants receiving combination antiretroviral therapy when indicated.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, symptomatic pulmonary fibrosis or interstitial pneumonitis, or
    psychiatric illness/social situations that, in the opinion of the investigator, may
    increase the risks associated with study participation or study treatment, or may
    interfere with the conduct of the study or the interpretation of the study results.

    - Receiving any other investigational agent which would be considered as a treatment
    for the primary neoplasm.

    - Other active malignancy 3 years prior to registration.

    EXCEPTIONS: Non-melanoma skin cancer, prostatic intraepithelial neoplasia without
    evidence of prostate cancer, lobular carcinoma in situ in one breast, or carcinoma-in-situ
    of the cervix that has been treated.

    - History of prior malignancy for which patient is receiving other specific treatment
    for their cancer.

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to irinotecan, cetuximab, and/or bevacizumab that led to discontinuation
    of those agents.

    - Significant history of bleeding events or pre-existing bleeding diathesis 6 months
    of randomization (unless the source of bleeding has been resected)

    - History of gastrointestinal perforation 12 months prior to randomization.

    3.29l Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled
    as indicated by baseline pattern of >3 loose stools daily in subjects without a colostomy
    or ileostomy. Subjects with a colostomy or ileostomy may be entered at investigator
    discretion.

    - Arterial thrombotic events 6 months prior to randomization Note: This includes
    transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or
    angina requiring surgical or medical intervention in the past 6 months, or myocardial
    infarction (MI).

    - Clinically significant peripheral artery disease (e.g., claudication with <1 block)
    or any other arterial thrombotic event.

    - Serious or non-healing wound, ulcer, or bone fracture.

    - History of hypertension not well-controlled (160/90) even though on a regimen of
    anti-hypertensive therapy.

    - Evidence of Gilbert's syndrome or known homozygosity for the UGT1A1*28 allele
    (special screening not required).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival

    Secondary Outcome Measures

    Trial Keywords