A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)
31. juli 2017 oppdatert av: Hoffmann-La Roche
Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study
This study will assess the efficacy and safety of two different neoadjuvant treatment approaches including bevacizumab in newly diagnosed participants with high risk locally advanced rectal cancer.
Participants will be randomized into one of two treatment arms (Arm A or Arm B).
Studieoversikt
Status
Fullført
Forhold
Studietype
Intervensjonell
Registrering (Faktiske)
91
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Angers, Frankrike, 49055
- ICO Paul Papin; Oncologie Medicale.
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Angers, Frankrike, 49055
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Besancon, Frankrike, 25030
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Besancon, Frankrike, 25030
- HOPITAL JEAN MINJOZ; Oncologie
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Bordeaux, Frankrike, 33075
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Bordeaux, Frankrike, 33075
- Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
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Dijon, Frankrike, 21079
- Centre Georges Francois Leclerc; Oncologie 3
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Dijon, Frankrike, 21079
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La Tronche, Frankrike, 38700
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La Tronche, Frankrike, 38700
- Hopital Albert Michallon; Radiotherapie
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Lille, Frankrike, 59020
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Lille, Frankrike, 59020
- Centre Oscar Lambret; Radiotherapie
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Montbeliard, Frankrike, 25209
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Montbeliard, Frankrike, 25209
- Centre Hospitalier Andre Boulloche; Departement D'Oncologie
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Montpellier, Frankrike, 34928
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Montpellier, Frankrike, 34928
- Centre Val Aurelle Paul Lamarque; Radiotherapie
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Nancy, Frankrike, 54100
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Nancy, Frankrike, 54100
- Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
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Nice, Frankrike, 06189
- Centre Antoine Lacassagne; Hopital De Jour A2
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Nice, Frankrike, 06189
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Paris, Frankrike, 75970
- HOPITAL TENON; Cancerologie Medicale
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Paris, Frankrike, 75970
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Paris, Frankrike, 75651
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Paris, Frankrike, 75475
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Paris, Frankrike, 75651
- Ch Pitie Salpetriere; Oncologie Medicale
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Paris, Frankrike, 75475
- Hopital Saint Louis; Radiotherapie Oncologie
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Pierre Benite, Frankrike, 69495
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Pierre Benite, Frankrike, 69495
- Ch Lyon Sud; Radiotherapie Sct Jules Courmont
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Poitiers, Frankrike, 86021
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Poitiers, Frankrike, 86021
- Chu La Miletrie; Radiotherapie
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Saint Herblain, Frankrike, 44805
- Ico Rene Gauducheau; Oncologie
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Saint Herblain, Frankrike, 44805
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Strasbourg, Frankrike, 67065
- Centre Paul Strauss; Oncologie Medicale
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Strasbourg, Frankrike, 67065
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Toulouse, Frankrike, 31078
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Toulouse, Frankrike, 31078
- Polyclinique Du Parc; Centre De Hautes Energies
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Tours, Frankrike, 37044
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Tours, Frankrike, 37044
- Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
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Vandoeuvre Les Nancy, Frankrike, 54511
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Vandoeuvre Les Nancy, Frankrike, 54511
- Centre Alexis Vautrin; Oncologie Medicale
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 75 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- histologically confirmed locally advanced rectal cancer;
- measurable disease;
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Exclusion Criteria:
- prior treatment with bevacizumab;
- prior radiotherapy to pelvic region, or previous cytotoxic chemotherapy;
- previous history of malignancy (other than basal and squamous cell cancer of the skin, or in situ cancer of the cervix);
- history or evidence of central nervous system (CNS) disease;
- clinically significant cardiovascular disease;
- chronic treatment with high dose aspirin (more than [>] 325 milligrams per day [mg/day]) or non-steroidal anti-inflammatory drugs.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Arm A (Bevacizumab, Induction Chemotherapy, Chemoradiotherapy)
In this arm, participants will undergo 3 phases of treatment.
During the Phase 1, participants will receive induction chemotherapy with 6 two-week cycles of bevacizumab + Folfox-4 (5-FU + oxaliplatin + folinic acid) for 12 weeks followed by a treatment-free interval of 3 to 4 weeks.
The Phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (intravenous [IV] infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks.
The Phase 3 will be surgery involving a radical rectal excision using the total mesorectal excision (TME) technique.
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Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
Andre navn:
Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m^2) as a 2-hour IV infusion.
Folinic acid will be administered at a dose of 200 mg/m^2 as a 2-hour infusion.
5-fluorouracil will be administered at a dose of 400 mg/m^2 as an IV bolus, then at a dose of 600 mg/m^2 as a continuous infusion for 22 hours in Phase 1, and will be administered at a dose of 225 mg/m^2 as a 24-hour infusion, 5 days a week, for 5 weeks in Phase 2.
Radiotherapy will be delivered in fraction of 1.8 gray per day (Gy/day), 5 days a week for 5 weeks, i.e., a total dose of 45 Gy will be administered in 25 fractions over a period of 33 days.
Radical rectal excision based on the TME technique.
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Eksperimentell: Arm B (Bevacizumab, Chemoradiotherapy)
In this arm, participants will receive the Phase 2 and Phase 3 treatments only.
The phase 2 will include 7 weeks of bevacizumab + chemoradiotherapy (IV infusion of bevacizumab alone, 2 weeks before administration of the first cycle of chemoradiotherapy, then 5 one-week cycles of chemoradiotherapy [5-FU + radiotherapy], with administration of bevacizumab every two weeks [Cycles 1, 3 and 5]) followed by a treatment-free interval of 6 to 8 weeks.
The phase 3 will be surgery involving a radical rectal excision using the TME technique.
|
Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
Andre navn:
5-fluorouracil will be administered at a dose of 400 mg/m^2 as an IV bolus, then at a dose of 600 mg/m^2 as a continuous infusion for 22 hours in Phase 1, and will be administered at a dose of 225 mg/m^2 as a 24-hour infusion, 5 days a week, for 5 weeks in Phase 2.
Radiotherapy will be delivered in fraction of 1.8 gray per day (Gy/day), 5 days a week for 5 weeks, i.e., a total dose of 45 Gy will be administered in 25 fractions over a period of 33 days.
Radical rectal excision based on the TME technique.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Tidsramme: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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Tumor sterilization was defined as the absence of residual tumor cells in the resected specimen including lymph nodes (ypT0-N0).
The rate of sterilization of the tumoral specimen was assessed after surgery on the surgical specimen by local review.
Analyses were performed for participants who have been operated as defined by the protocol (within the study and TME technique) and for all participants who have been operated.
Reported is the percentage of participants with tumor sterilization.
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After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
Tidsramme: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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A participant with a downstaging was defined as a participant with T3 (T describes the size of the original [primary] tumor) at inclusion and T2 or T1 or T0 after surgery, or with N+ (N describes lymph nodes involvement) at inclusion and N- after surgery and if T is equal at inclusion and after surgery.
The clinical tumor-node-metastasis (cTNM) classification was used at inclusion and the pathological staging tumor and nodes (ypTN) classification after surgery.
Reported is the percentage of participants with tumor downstaging of the surgical specimen according to the local review and centralized review.
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After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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Percentage of Participants With Local and Distant Recurrences
Tidsramme: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).
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After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
Tidsramme: Baseline up to approximately 6 years
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Baseline up to approximately 6 years
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Disease-Free Survival (DFS)
Tidsramme: From first time of the treatment administration to the date of second cancer, local or regional recurrence, distant metastasis or death from any cause (up to approximately 6 years)
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The DFS was defined as the time from the first treatment intake to disease recurrence assessed (second primary cancer, local or distant recurrence, distant metastases) or death from any cause.
The DFS was analyzed using Kaplan-Meier method.
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From first time of the treatment administration to the date of second cancer, local or regional recurrence, distant metastasis or death from any cause (up to approximately 6 years)
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Percentage of Participants Who Died
Tidsramme: Baseline up to approximately 6 years
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Baseline up to approximately 6 years
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Overall Survival
Tidsramme: From the first treatment administration to the date of death (up to approximately 6 years)
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The overall survival was defined as the time from the first treatment intake to death from any cause.
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From the first treatment administration to the date of death (up to approximately 6 years)
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Number of Cycles of Induction Chemotherapy
Tidsramme: 6 cycles (12 weeks; cycle length = 14 days)
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6 cycles (12 weeks; cycle length = 14 days)
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Number of Cycles of Chemotherapy
Tidsramme: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
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Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
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Number of Cycles of Radiotherapy
Tidsramme: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
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Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
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Percentage of Participants With Surgery
Tidsramme: Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment
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The surgery involving a radical rectal excision using the TME technique.
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Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
23. oktober 2007
Primær fullføring (Faktiske)
23. mars 2016
Studiet fullført (Faktiske)
23. mars 2016
Datoer for studieregistrering
Først innsendt
18. mars 2009
Først innsendt som oppfylte QC-kriteriene
18. mars 2009
Først lagt ut (Anslag)
19. mars 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
4. august 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
31. juli 2017
Sist bekreftet
1. juli 2017
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Neoplasmer
- Neoplasmer etter nettsted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Tarmsykdommer
- Intestinale neoplasmer
- Rektale sykdommer
- Kolorektale neoplasmer
- Rektale neoplasmer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Beskyttende agenter
- Antineoplastiske midler, immunologiske
- Angiogenese-hemmere
- Angiogenesemodulerende midler
- Vekststoffer
- Veksthemmere
- Mikronæringsstoffer
- Vitaminer
- Motgift
- Vitamin B kompleks
- Hematinikk
- Fluorouracil
- Oksaliplatin
- Bevacizumab
- Leucovorin
- Levoleucovorin
- Folsyre
Andre studie-ID-numre
- ML19202
- 2006-003472-35 (EudraCT-nummer)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .