Clinical Trials /

FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer

NCT02508077

Description:

This phase II trial studies how well fluorouracil, leucovorin calcium, and irinotecan hydrochloride (FOLFIRI) together with panitumumab work in treating patients with colorectal cancer that expresses the RAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF) wild-type genes, has spread from the original site of growth to another part of the body (metastatic), resists the effects of treatment with prior cetuximab (or panitumumab) plus irinotecan hydrochloride-based therapy, and who have failed at least one subsequent non-anti-epidermal growth factor receptor (EGFR) containing treatment regimen. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as panitumumab, may block tumor growth in different ways by targeting certain cells. Giving FOLFIRI together with panitumumab may be an effective treatment for colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">FOLFIRI</span> and <span class="go-doc-concept go-doc-intervention">Panitumumab</span> in Treating Patients With <span class="go-doc-concept go-doc-biomarker">RAS</span> and <span class="go-doc-concept go-doc-biomarker">BRAF</span> Wild-Type Metastatic <span class="go-doc-concept go-doc-disease">Colorectal Cancer</span>

Title

  • Brief Title: FOLFIRI and Panitumumab in Treating Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer
  • Official Title: A Prospective Study of FOLFIRI Plus Panitumumab in Extended RAS Wild Type and BRAF Wild Type Metastatic Colorectal Cancer With Acquired Resistance to Prior Cetuximab (or Panitumumab) Plus Irinotecan-Based Therapy and Who Failed at Least One Subsequent Non-anti-EGFR Containing Regimen
  • Clinical Trial IDs

    NCT ID: NCT02508077

    ORG ID: 15117

    NCI ID: NCI-2015-01241

    Trial Conditions

    Recurrent Colorectal Carcinoma

    Stage IVA Colorectal Cancer

    Stage IVB Colorectal Cancer

    Trial Interventions

    Drug Synonyms Arms
    Fluorouracil 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Actino-Hermal, Adrucil, Arumel, Cytosafe, Efudex, Efurix, Fiverocil, Fluoro Uracil, Fluoroplex, FLUOROURACIL, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Flurox, Ribofluor, Ro 2-9757, Ro-2-9757, Timazin Treatment (panitumumab and FOLFIRI)
    Irinotecan Hydrochloride Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, IRINOTECAN HYDROCHLORIDE, U-101440E Treatment (panitumumab and FOLFIRI)
    Leucovorin Calcium Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, LEUCOVORIN CALCIUM, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin Treatment (panitumumab and FOLFIRI)

    Trial Purpose

    This phase II trial studies how well fluorouracil, leucovorin calcium, and irinotecan
    hydrochloride (FOLFIRI) together with panitumumab work in treating patients with colorectal
    cancer that expresses the RAS and B-Raf proto-oncogene, serine/threonine kinase (BRAF)
    wild-type genes, has spread from the original site of growth to another part of the body
    (metastatic), resists the effects of treatment with prior cetuximab (or panitumumab) plus
    irinotecan hydrochloride-based therapy, and who have failed at least one subsequent
    non-anti-epidermal growth factor receptor (EGFR) containing treatment regimen. Drugs used in
    chemotherapy, such as fluorouracil, leucovorin calcium, and irinotecan hydrochloride, work
    in different ways to stop the growth of tumor cells, either by killing the cells, by
    stopping them from dividing, or by stopping them from spreading. Giving more than one drug
    (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as
    panitumumab, may block tumor growth in different ways by targeting certain cells. Giving
    FOLFIRI together with panitumumab may be an effective treatment for colorectal cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Estimate the response rate (RR) and progression-free survival (PFS) with FOLFIRI +
    panitumumab in patients with acquired resistance to panitumumab (or cetuximab) + irinotecan
    (irinotecan hydrochloride)-based therapy after a documented clinical response or prolonged
    PFS and following progression on a subsequent non-anti-EGFR containing regimen in extended
    RAS wild-type and BRAF wild-type patients.

    SECONDARY OBJECTIVES:

    I. Estimate the overall survival (OS) in the re-challenge populations. II. Describe the
    safety of re-challenge in this population. III. Investigate the impact of PFS, RR on prior
    anti-EGFR + irinotecan-based exposure on the response and PFS on the current study.

    TERTIARY OBJECTIVES:

    I. Collect serial plasma samples to investigate the incidence of RAS and BRAF mutation in
    circulating free deoxyribonucleic acid (DNA) at baseline, every 2 months, and at the time to
    progression (and following progression when feasible).

    II. Collect serial plasma samples for future biomarker exploration, including the potential
    investigation of micro-ribonucleic acid (RNA).

    OUTLINE:

    Patients receive panitumumab intravenously (IV) over 30-90 minutes, irinotecan hydrochloride
    IV over 90 minutes, leucovorin calcium orally (PO), and fluorouracil IV over 46 hours on day
    1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable
    toxicity.

    After completion of study treatment, patients are followed up at 30 days and then every 3
    months thereafter.

    Trial Arms

    Name Type Description Interventions
    Treatment (panitumumab and FOLFIRI) Experimental Patients receive panitumumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium PO, and fluorouracil IV over 46 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Fluorouracil, Irinotecan Hydrochloride, Leucovorin Calcium

    Eligibility Criteria

    Inclusion Criteria:

    - Participant must have the ability to understand and the willingness to sign a written
    informed consent document

    - Participant must be willing to comply with study and/or follow-up procedures

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-2

    - Life expectancy of 3 >= months

    - Histologically confirmed metastatic colon or rectal cancer

    - Extended RAS and BRAF wild type status documented on archival tumor tissue or on
    fresh biopsy if no archival tissue present

    - Measurable disease defined by at least 1 lesion >= 1 cm

    - Documented objective response or stable disease lasting for 6 months or more to last
    prior anti-EGFR (cetuximab or panitumumab) in combination with irinotecan or FOLFIRI

    - Progression within 6 weeks following their last dose of anti-EGFR therapy

    - Treatment with a non-EGFR targeting regimen following progression on anti-EGFR plus
    irinotecan-based therapy

    - At least 4 months from prior anti-EGFR therapy prior to start of study treatment

    - At least three weeks from any non-anti-EGFR therapy prior to start of study
    treatment; any number of prior therapies is permitted

    - Adequate recovery in the investigators opinion from any clinically significant
    toxicity from prior therapy

    - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

    - Hemoglobin (Hgb) >= 9 g/dL without transfusions

    - Platelets (PLT) >= 100 x 10^9/L without transfusions

    - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])
    and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 2.5 x upper limit of normal (ULN); patient with liver metastases =< 5 x ULN

    - Total bilirubin =< ULN

    - Creatinine =< 1.5 mg/dL

    - Magnesium >= 1.2mg/dL or 0.5 mmol/L

    - Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of
    childbearing potential only), to be performed locally within the screening period

    - Agreement by females of childbearing potential and sexually active males to use an
    effective method of contraception (hormonal or barrier method of birth control or
    abstinence) prior to study entry and for three months following duration of study
    participation; should a woman become pregnant or suspect that she is pregnant while
    participating on the trial, she should inform her treating physician immediately

    Exclusion Criteria:

    - History of severe anti-EGFR toxicity requiring drug discontinuation or
    dose-modification within the first 4 months of prior anti-EGFR therapy

    - History of intolerance to irinotecan at dose-intensity of 125 mg/m^2/2 weeks or lower

    - History of intolerance to 5-FU at dose-intensity of 1800 mg/m^2/2 weeks or lower

    - Current use (or planned use during the treatment period) of other investigational
    agents, or biological, chemotherapy, radiation or other anti-tumor therapy

    - Co-medication that may interfere with study results; e.g. immuno-suppressive agents
    other than corticosteroids, such as systemic cyclosporine and tacrolimus

    - No St John's wort supplement or other herbal supplementation is allowed while on
    trial; patients are not to take grapefruit juice during study treatment

    - Use of drugs known to inhibit UDP glycosyltransferase 1 family, polypeptide A1 gene
    (UGT1A1), such as Atazanavir, Gemfibrozil, Indinavir, or Ketoconazole while on study
    treatment; (patients using these drugs must not take these drugs on the day study
    treatment begins and for the duration of study treatment)

    - Planned use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
    inhibitors or CYP3A4 inducers while on study treatment unless deemed clinically
    necessary with no reasonable alternatives and with expressed permission from the
    principal investigator

    - If on anticoagulation, participant must be on stable therapeutic dose prior to
    enrollment

    - Impairment of gastrointestinal function or gastrointestinal disease (e.g., active
    ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
    extensive small bowel resection)

    - Major surgery =< 3 weeks prior to starting study drug or who have not recovered from
    side effects of such procedure

    - Unstable pulmonary embolism, deep vein thrombosis, or other significant
    arterial/venous thromboembolic event =< 30 days before enrollment

    - Clinically significant cardiovascular disease (including myocardial infarction,
    unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
    arrhythmia) =< 6 months prior to enrollment

    - History of interstitial lung disease (ILD) eg, interstitial pneumonitis, pulmonary
    fibrosis or evidence of ILD on baseline chest computed tomography (CT) or magnetic
    resonance imaging (MRI)

    - Other active malignancies except cervical carcinomas in situ or clinically
    insignificant non-melanoma skin cancers

    - Clinically significant uncontrolled illness or active infections

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to irinotecan, 5-FU, leucovorin or any of the products to be administered
    during dosing

    - Pregnant women and women who are lactating; breastfeeding should be discontinued if
    the mother is enrolled on this study

    - Any other condition that would, in the Investigator's judgment, contraindicate the
    patient's participation in the clinical study due to safety concerns or compliance
    with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,
    unable to swallow medication, social/psychological issues, etc

    - Prospective participants who, in the opinion of the investigator, may not be able to
    comply with all study procedures (including compliance issues related to
    feasibility/logistics)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS assessed by the revised RECIST guideline (version 1.1)

    RR assessed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

    Secondary Outcome Measures

    Impact of PFS on prior anti-EGFR therapy

    Impact of response on prior anti-EGFR therapy

    Impact of time since last anti-EGFR exposure on the PFS

    Impact of time since last anti-EGFR exposure on the RR

    Trial Keywords