A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)
Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Studientyp
Studientyp
Einschreibung (Tatsächlich)
Einschreibung
Phase
Phase
- Phase 2
Kontakte und Standorte
Studienorte
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Angers, Frankreich, 49055
- ICO Paul Papin; Oncologie Medicale.
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Angers, Frankreich, 49055
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Besancon, Frankreich, 25030
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Besancon, Frankreich, 25030
- HOPITAL JEAN MINJOZ; Oncologie
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Bordeaux, Frankreich, 33075
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Bordeaux, Frankreich, 33075
- Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
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Dijon, Frankreich, 21079
- Centre Georges Francois Leclerc; Oncologie 3
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Dijon, Frankreich, 21079
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La Tronche, Frankreich, 38700
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La Tronche, Frankreich, 38700
- Hopital Albert Michallon; Radiotherapie
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Lille, Frankreich, 59020
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Lille, Frankreich, 59020
- Centre Oscar Lambret; Radiotherapie
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Montbeliard, Frankreich, 25209
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Montbeliard, Frankreich, 25209
- Centre Hospitalier Andre Boulloche; Departement D'Oncologie
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Montpellier, Frankreich, 34928
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Montpellier, Frankreich, 34928
- Centre Val Aurelle Paul Lamarque; Radiotherapie
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Nancy, Frankreich, 54100
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Nancy, Frankreich, 54100
- Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
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Nice, Frankreich, 06189
- Centre Antoine Lacassagne; Hopital De Jour A2
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Nice, Frankreich, 06189
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Paris, Frankreich, 75970
- HOPITAL TENON; Cancerologie Medicale
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Paris, Frankreich, 75970
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Paris, Frankreich, 75651
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Paris, Frankreich, 75475
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Paris, Frankreich, 75651
- Ch Pitie Salpetriere; Oncologie Medicale
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Paris, Frankreich, 75475
- Hopital Saint Louis; Radiotherapie Oncologie
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Pierre Benite, Frankreich, 69495
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Pierre Benite, Frankreich, 69495
- Ch Lyon Sud; Radiotherapie Sct Jules Courmont
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Poitiers, Frankreich, 86021
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Poitiers, Frankreich, 86021
- Chu La Miletrie; Radiotherapie
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Saint Herblain, Frankreich, 44805
- Ico Rene Gauducheau; Oncologie
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Saint Herblain, Frankreich, 44805
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Strasbourg, Frankreich, 67065
- Centre Paul Strauss; Oncologie Medicale
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Strasbourg, Frankreich, 67065
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Toulouse, Frankreich, 31078
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Toulouse, Frankreich, 31078
- Polyclinique Du Parc; Centre De Hautes Energies
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Tours, Frankreich, 37044
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Tours, Frankreich, 37044
- Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
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Vandoeuvre Les Nancy, Frankreich, 54511
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Vandoeuvre Les Nancy, Frankreich, 54511
- Centre Alexis Vautrin; Oncologie Medicale
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Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Anzahl der Arme
Waffen und Interventionen
Teilnehmergruppe / ArmTeilnehmergruppe / Arm |
Intervention / BehandlungIntervention / Behandlung |
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Experimental: 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.
Andere Namen:
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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Experimental: 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.
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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.
Andere Namen:
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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Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Zeitfenster: 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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Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Baseline up to approximately 6 years
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Baseline up to approximately 6 years
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Disease-Free Survival (DFS)
Zeitfenster: 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
Zeitfenster: Baseline up to approximately 6 years
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Baseline up to approximately 6 years
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Overall Survival
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Sponsor
Sponsor
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Studienbeginn
Primärer Abschluss (Tatsächlich)
Primärer Abschluss
Studienabschluss (Tatsächlich)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- Neubildungen
- Neubildungen nach Standort
- Gastrointestinale Neubildungen
- Neoplasmen des Verdauungssystems
- Magen-Darm-Erkrankungen
- Darmerkrankungen
- Darmtumoren
- Rektale Erkrankungen
- Kolorektale Neubildungen
- Rektale Neoplasien
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Schutzmittel
- Antineoplastische Mittel, immunologische
- Angiogenese-Inhibitoren
- Angiogenese-modulierende Mittel
- Wuchsstoffe
- Wachstumshemmer
- Mikronährstoffe
- Vitamine
- Gegenmittel
- Vitamin B-Komplex
- Hämatitik
- Fluorouracil
- Oxaliplatin
- Bevacizumab
- Leucovorin
- Levoleucovorin
- Folsäure
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- ML19202
- 2006-003472-35 (EudraCT-Nummer)
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