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A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer (INOVA)

31 juillet 2017 mis à jour par: 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).

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

91

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • France
      • Angers, France, 49055
        • ICO Paul Papin; Oncologie Medicale.
      • Angers, France, 49055
      • Besancon, France, 25030
      • Besancon, France, 25030
        • HOPITAL JEAN MINJOZ; Oncologie
      • Bordeaux, France, 33075
      • Bordeaux, France, 33075
        • Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale
      • Dijon, France, 21079
        • Centre Georges Francois Leclerc; Oncologie 3
      • Dijon, France, 21079
      • La Tronche, France, 38700
      • La Tronche, France, 38700
        • Hopital Albert Michallon; Radiotherapie
      • Lille, France, 59020
      • Lille, France, 59020
        • Centre Oscar Lambret; Radiotherapie
      • Montbeliard, France, 25209
      • Montbeliard, France, 25209
        • Centre Hospitalier Andre Boulloche; Departement D'Oncologie
      • Montpellier, France, 34928
      • Montpellier, France, 34928
        • Centre Val Aurelle Paul Lamarque; Radiotherapie
      • Nancy, France, 54100
      • Nancy, France, 54100
        • Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE
      • Nice, France, 06189
        • Centre Antoine Lacassagne; Hopital De Jour A2
      • Nice, France, 06189
      • Paris, France, 75970
        • HOPITAL TENON; Cancerologie Medicale
      • Paris, France, 75970
      • Paris, France, 75651
      • Paris, France, 75475
      • Paris, France, 75651
        • Ch Pitie Salpetriere; Oncologie Medicale
      • Paris, France, 75475
        • Hopital Saint Louis; Radiotherapie Oncologie
      • Pierre Benite, France, 69495
      • Pierre Benite, France, 69495
        • Ch Lyon Sud; Radiotherapie Sct Jules Courmont
      • Poitiers, France, 86021
      • Poitiers, France, 86021
        • Chu La Miletrie; Radiotherapie
      • Saint Herblain, France, 44805
        • Ico Rene Gauducheau; Oncologie
      • Saint Herblain, France, 44805
      • Strasbourg, France, 67065
        • Centre Paul Strauss; Oncologie Medicale
      • Strasbourg, France, 67065
      • Toulouse, France, 31078
      • Toulouse, France, 31078
        • Polyclinique Du Parc; Centre De Hautes Energies
      • Tours, France, 37044
      • Tours, France, 37044
        • Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie
      • Vandoeuvre Les Nancy, France, 54511
      • Vandoeuvre Les Nancy, France, 54511
        • Centre Alexis Vautrin; Oncologie Medicale

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Bevacizumab
Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
Autres noms:
  • Avastin
Médicament: Oxaliplatin
Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m^2) as a 2-hour IV infusion.
Médicament: Folinic Acid
Folinic acid will be administered at a dose of 200 mg/m^2 as a 2-hour infusion.
Médicament: 5-fluorouracil
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.
Radiation: Preoperative Radiotherapy
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.
Procédure: Surgery
Radical rectal excision based on the TME technique.
Expérimental: 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.
Médicament: Bevacizumab
Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
Autres noms:
  • Avastin
Médicament: 5-fluorouracil
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.
Radiation: Preoperative Radiotherapy
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.
Procédure: Surgery
Radical rectal excision based on the TME technique.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With Tumor Sterilization Defined by ypT0-N0
Délai: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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.
After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With Tumor Down-Staging (ypT0-pT2)
Délai: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
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.
After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Percentage of Participants With Local and Distant Recurrences
Délai: After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).
After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death
Délai: Baseline up to approximately 6 years
Baseline up to approximately 6 years
Disease-Free Survival (DFS)
Délai: 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)
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.
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)
Percentage of Participants Who Died
Délai: Baseline up to approximately 6 years
Baseline up to approximately 6 years
Overall Survival
Délai: From the first treatment administration to the date of death (up to approximately 6 years)
The overall survival was defined as the time from the first treatment intake to death from any cause.
From the first treatment administration to the date of death (up to approximately 6 years)
Number of Cycles of Induction Chemotherapy
Délai: 6 cycles (12 weeks; cycle length = 14 days)
6 cycles (12 weeks; cycle length = 14 days)
Number of Cycles of Chemotherapy
Délai: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Number of Cycles of Radiotherapy
Délai: Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Percentage of Participants With Surgery
Délai: Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment
The surgery involving a radical rectal excision using the TME technique.
Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hoffmann-La Roche

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

23 octobre 2007

Achèvement primaire (Réel)

23 mars 2016

Achèvement de l'étude (Réel)

23 mars 2016

Dates d'inscription aux études

Première soumission

18 mars 2009

Première soumission répondant aux critères de contrôle qualité

18 mars 2009

Première publication (Estimation)

19 mars 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

4 août 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

31 juillet 2017

Dernière vérification

1 juillet 2017

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • ML19202
  • 2006-003472-35 (Numéro EudraCT)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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