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Cetuximab and Bevacizumab as First-Line Therapy Followed By Combination Chemotherapy and Bevacizumab With or Without Cetuximab as Second-Line Therapy in Treating Patients With Stage IV Colorectal Cancer

1. juli 2016 opdateret af: Alliance for Clinical Trials in Oncology

Randomized Phase II Trial of Cetuximab/Bevacizumab (CB) as Palliative First-Line Therapy in Patients With Advanced Colorectal Cancer Followed by FOLFOX+CB vs. FOLFOX+B

RATIONALE: Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibodies together with combination chemotherapy may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving cetuximab together bevacizumab works as first-line therapy, followed by combination chemotherapy and bevacizumab with or without cetuximab as second-line therapy in treating patients with stage IV colorectal cancer.

Studieoversigt

Status

Trukket tilbage

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

OBJECTIVES:

Primary

  • To assess the efficacy of bevacizumab and cetuximab as first-line treatment for metastatic colorectal cancer, as measured by percentage of patients who remain progression-free at 6 months.

Secondary

  • To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients treated with bevacizumab and cetuximab.
  • To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients who are refractory to dual-agent bevacizumab and cetuximab and are subsequently treated with modified FOLFOX7 chemotherapy and bevacizumab with or without cetuximab.
  • To evaluate quality of life parameters in patients treated with these regimens.
  • To estimate the direct medical resource utilization and costs.
  • To assess the reliability of FDG-PET as a measurement of early treatment response, as measured by percentage of patients who are progression-free at 6 months.
  • To identify circulating angiogenesis biomarkers.
  • To assay the activity of pro-angiogenic factors in plasma angiogenic assays.

OUTLINE: This is a multicenter study*. Patients are stratified according to ECOG performance status (0-1 vs 2) and number of metastatic sites (1 vs > 1).

NOTE: *Participating site must be PET-qualified.

  • First-line therapy: Patients receive bevacizumab IV over 30-90 minutes and cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease proceed to second-line therapy.

  • Second-line therapy: Patients are randomized* to 1 of 2 treatment arms.

    • Arm I (modified FOLFOX7 with bevacizumab only): Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
    • Arm II (modified FOLFOX7 with bevacizumab and cetuximab): Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Randomization occurs prior to receiving first-line therapy.

Patients undergo blood sample collection periodically for translational studies. Samples are analyzed for circulating endothelial cells and endothelial progenitor cells via flow cytometry; angiogenic activity of serum/plasma in angiogenesis-dependent diseases via endothelial proliferation assay and matrigel tube formation assay; and circulating angiogenesis biomarkers (i.e., free VEGF, soluble FLT-1, and KDR) via ELISA.

Quality of life is assessed periodically using the UNISCALE, Skindex-16, and Skin Assessment Questionnaires.

After completion of study treatment, patients are followed every 6 months for up to 3 years.

Undersøgelsestype

Interventionel

Fase

  • Fase 2

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage IV colorectal cancer
  • Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
  • Must not be a candidate for neoadjuvant therapy
  • No CNS or brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • AST ≤ 3 times ULN
  • Creatinine ≤ 1.5 x times ULN
  • Proteinuria < 1+ by urinalysis OR proteinuria < 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • English-speaking patients must have the ability to complete questionnaires by themselves or with assistance
  • Must be willing to provide blood and tissue samples for research purposes
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No blood pressure > 150/100 mm Hg
  • No New York Heart Association (NYHA) class II-IV congestive heart failure
  • No myocardial infarction or unstable angina within the past 6 months
  • No stroke or transient ischemic attack within the past 6 months
  • No clinically significant vascular disease (e.g., aortic aneurysm or aortic dissection)
  • No clinically significant peripheral vascular disease
  • No evidence of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 28 days
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious nonhealing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

  • No prior nonsurgical treatment for stage IV disease

    • Adjuvant therapy allowed if completed > 6 months prior to study registration
  • More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study
  • No prior therapy that specifically and directly targets the EGFR pathway
  • No prior monoclonal antibody therapy
  • More than 28 days since prior major surgery or open biopsy

  • More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies

    • Placement of a vascular access device does not have to meet this criterion
  • No concurrent major surgery

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: Arm I (second-line therapy)
Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biologisk: bevacizumab
Givet IV
Medicin: oxaliplatin
Givet IV
Medicin: leucovorin calcium
Givet IV
Medicin: fluorouracil
Givet IV
Eksperimentel: Arm II (second-line therapy)
Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biologisk: bevacizumab
Givet IV
Medicin: oxaliplatin
Givet IV
Medicin: leucovorin calcium
Givet IV
Medicin: fluorouracil
Givet IV
Biologisk: cetuximab
Givet IV

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Progression-free survival (PFS) rate at 6 months
Tidsramme: at 6 months
at 6 months

Sekundære resultatmål

Resultatmål
Tidsramme
Livskvalitet
Tidsramme: op til 3 år
op til 3 år
Varighed af svar
Tidsramme: op til 3 år
op til 3 år
Tumor response rate associated with second-line therapy
Tidsramme: up to 3 years
up to 3 years
Time to progression during second-line therapy
Tidsramme: up to 3 years
up to 3 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Alliance for Clinical Trials in Oncology

Samarbejdspartnere

National Cancer Institute (NCI)

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Datoer for studieregistrering

Først indsendt

11. december 2007

Først indsendt, der opfyldte QC-kriterier

11. december 2007

Først opslået (Skøn)

12. december 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

6. juli 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. juli 2016

Sidst verificeret

1. juli 2016

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • N0548
  • CDR0000578111 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-2009-00651 (Registry Identifier: CTRP (Clinical Trials Reporting System))

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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