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Avastin in Combination With Chemotherapy for RAS Mutant Unresectable Colorectal Liver-limited Metastases

15. december 2019 opdateret af: Xu jianmin

Study of Avastin in Combination With Chemotherapy for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases

In this study, the investigators assessed the effect of avastin in combination with chemotherapy in the treatment of RAS mutant-type, unresectable colorectal liver-limited metastases

Studieoversigt

Status

Afsluttet

Intervention / Behandling

Detaljeret beskrivelse

Patients will be eligible for inclusion if the patients have histologically confirmed colorectal adenocarcinoma with RAS mutant liver-confined metastases deemed non-resectable. Eligible patients will be randomly assigned to chemotherapy plus avastin (arm A) or chemotherapy alone (arm B). Treatment will continue until tumor response indicates suitability for surgery for liver metastases or until disease progression or unacceptable toxic effects. The primary endpoint is the conversion rate to radical resection for liver metastases,which will be assessed by local multidisciplinary team (includes more than three liver surgeons and one radiologist) with the use of contrast-enhanced CT or MRI after 4 cycles and then every other 4 cycles up to 12 cycles. To provide an objective assessment of changes in resectability, radiological images will be presented by a radiologist to more than 3 liver surgeons, who are blinded to the clinical data. Patients will be considered resectable if 50% or more of surgeons vote for radical resection of LM. For patients whose liver-metastases are assessed resectable, resection should be scheduled to be performed within 2~3 weeks of the last treatment cycle. Following resection, patients will be advised to continue the same therapeutic regimen until the treatments reach a sum of 12 cycles.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

241

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Shanghai
      • Shanghai, Shanghai, Kina, 200000
        • Zhongshan Hospital, Fudan University

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 til 75 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Age ≥ 18 and ≤ 75 years;
  2. Primary tumour was histologically confirmed colorectal adenocarcinoma;
  3. Together with clinical or radiological evidence of first occurrence of non-resectable liver-only metastases
  4. With evidence of tumor RAS gene mutant status;
  5. With at least one measurable tumor.
  6. Performance status (ECOG) 0~1
  7. A life expectancy of ≥ 3 months
  8. Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization)
  9. Adequate hepatic and renal function: Serum bilirubin≤1.5 x upper limit of normal (ULN), alkaline phosphatase ≤5x ULN, and serum transaminase (either AST or ALT) ≤ 5 x ULN(within 1 week prior to randomization);
  10. Written informed consent for participation in the trial.

Exclusion Criteria:

  1. Previous exposure to target therapy, chemotherapy, radiotherapy or intervention therapy for colorectal liver metastases.
  2. Known or suspected extrahepatic metastases.
  3. Patients with known hypersensitivity reactions to any of the components of the study treatments.
  4. Having previously participated in a study which included a possibility of being allocated to avastin therapy (whether or not the patient actually received avastin)
  5. Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months or left ventricular ejection fraction (LVEF) below the institutional range of normal
  6. Acute or sub-acute intestinal occlusion
  7. Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding
  8. Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
  9. Known drug abuse/ alcohol abuse
  10. Legal incapacity or limited legal capacity
  11. Pre-existing peripheral neuropathy.

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
Eksperimentel: ARM A
patients received avastin in combination with mFOLFOX6
Drug: avastin On day 1 of a 14 day treatment cycle, patients received a 2-hour infusion of avastin (5mg/kg) followed by chemotherapy of mFOLFOX6 until progressive disease or unacceptable toxicity.
Andre navne:
  • Bevacizumab
mFOLFOX-6 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV400mg/m2 on days 1 infused during 2 hours, followed by FU 400 mg/m2 intravenous bolus then 2400 mg/m2 continuous infusion for 46 hours)
Aktiv komparator: ARM B
Patients received mFOLFOX6 alone
mFOLFOX-6 (oxaliplatin, 85mg/m2 on day 1 infused during 2 hours;LV400mg/m2 on days 1 infused during 2 hours, followed by FU 400 mg/m2 intravenous bolus then 2400 mg/m2 continuous infusion for 46 hours)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
the rate of patients converted to resection for liver metastases
Tidsramme: 3 years
To explore whether avastin in combination with chemotherapy as treatment could improve the resection rate in patients with RAS mutant-type, unresectable colorectal liver-limited metastases compared with chemotherapy alone.
3 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
progression free survival
Tidsramme: 3 years
PFS will be defined as the period from the first day of avastin treatment or chemotherapy to the date of disease progression (PD) or to death. Patients without PD who discontinued the study for any reason is censored at the last on-study tumor assessment date.or distant(i.e. metastasis) disease recurrence or death.
3 years
overall survival
Tidsramme: 3 years
OS will be calculated from randomization to death from any cause or the date of the last follow-up, at which point the data will be censored.
3 years
tumor response
Tidsramme: 3 years
3 years

Samarbejdspartnere og efterforskere

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

Sponsor

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

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.

Studer store datoer

Studiestart (Faktiske)

1. oktober 2013

Primær færdiggørelse (Faktiske)

1. december 2017

Studieafslutning (Faktiske)

1. juni 2019

Datoer for studieregistrering

Først indsendt

23. september 2013

Først indsendt, der opfyldte QC-kriterier

29. oktober 2013

Først opslået (Skøn)

30. oktober 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

17. december 2019

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. december 2019

Sidst verificeret

1. december 2019

Mere information

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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